Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Indian Consensus on the Role and Position of Angiotensin Receptor-neprilysin Inhibitors in the Management of Heart Failure.

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Shared Decision-Making, Advance Care Planning for Chronic Kidney Disease Patients.

Advance care planning (ACP) is a process by which clinicians together with patients and families reflect on and outline care goals to inform current and future care. ACP or shared decision-making is not only about key medical decisions, such as decision about continuing dialysis, or agreement for "not for resuscitation" order when in hospital. The importance of its role in chronic kidney disease (CKD) patients is less known and not being well practiced in our country. When done well, it involves enhancement of final days, weeks, and months with positive decisions about family relationships, resolution of conflict, and living well until end of life, improved quality of life, decreased anxiety and depression among family members, reduced hospitalizations, increased uptake of hospice and palliative care services, and care that concurs with patient preferences. It lays out a set of relationships, values, and processes for approaching end-of-life decisions for the patient. It also includes attention to ethical, psychosocial, and spiritual issues relating to starting, continuing, withholding, and stopping dialysis. This workshop was done to sensitize ACP as a standard of care intervention in the management of CKD in our country.

Screening for Hypertension in Asymptomatic Individuals in India: An Expert Consensus Statement.

INTRODUCTION: Hypertension (HTN) is a rapidly growing epidemic in India. It is no larger restricted to older adults as more young Indians are being diagnosed with HTN. Despite its significant prevalence, the awareness, treatment, and control of HTN remain low in India. Thus, early diagnosis is essential to control HTN and prevent future complications. Screening for HTN can help identify undiagnosed and asymptomatic HTN, and thereby the early use of interventions to control the blood pressure (BP). However, no comprehensive guidelines have been established for effective HTN screening in asymptomatic individuals in an Indian setting. OBJECTIVE: To provide consensus recommendations for hypertension screening in India. CONSENSUS RECOMMENDATIONS: Screening for HTN can provide more effective control of HTN and reduce the complications. Experts recommended that the initial age at screening should be 18 years. In individuals at a high risk of HTN, targeted screening can be undertaken. BP measurement using an electronic BP recorder (with at least two readings) are required for identifying HTN during screening. In asymptomatic adults with BP <130/85 mmHg and BP of 130-139/85- 89 mmHg, rescreening should be conducted every 3-5 years and at least every year, respectively. Screening for HTN can be cost effective even when universal screening of the entire population is undertaken. CONCLUSION: The consensus recommendations would increase the awareness of HTN screening. Screening for HTN can provide more effective control of HTN and reduce the complications.

Catheter Related Right Atrial Thrombus in Patients on Maintenance Hemodialysis: Results of a Single Centre Retrospective Study from a Tertiary Care Hospital.

OBJECTIVE: To study the magnitude of the complication of catheter associated right atrial thrombus (CRAT) in patients with tunnelled central venous hemodialysis catheters (THC) for maintenance hemodialysis (MHD). MATERIAL AND METHODS: A retrospective study was conducted among patients with end stage kidney disease (ESKD) with THC for MHD who had undergone screening for CRAT with a 2D-echo (2DE) just before removal of the THC. The occurrence of CRAT and other clinical parameters were documented in these patients. RESULTS: A total of 28 patients (mean [SD] age 51 [15.2] years; females 17 [60.7%]) were included in the study. CRAT was observed in 5 (17.9%) patients. There was no difference in mean age in patients with or without thrombus (48±13.02 vs 51.61 ± 15.78 years; p = 0.61). History of diabetes and hypertension was present in 2 and all 5 patients respectively. There was no significant difference in the period the THC was in place in patients with or without CRAT (13±7.8 months vs 10.57±5.66 months; p = 0.54). There was no association between catheter related blood stream infection (CRBSI) and CRAT (p= 0.29). CONCLUSION: The incidence of CRAT in patients with THC for MHD was 17.9%. Patients with THC for MHD should be examined for presence of CRAT before removal of THC to prevent fatal pulmonary thromboembolism.

A prospective, multi-centre, observational study to examine kidney disease progression in adults with chronic kidney disease - CKDOD - Study design and preliminary results.

BACKGROUND: The objective of this article is to describe the organisation of an international, clinical registry, the Chronic Kidney Disease Observational Database (CKDOD), the processes of enrolling patients and entering data and preliminary results to date. DESIGN: The Chronic Kidney Disease Observational Database (CKDOD) is designed to assess the association between different factors with a known influence on chronic kidney disease (CKD) progression as well as treatment strategies such as dietary modifications, blood pressure control and pharmacological interventions in Asian countries (India, China, Malaysia and Thailand). The only inclusion criterion is the presence of CKD stage 2 or higher as defined by the KDIGO guidelines. Demographic and clinical information are collected by a standardised electronic questionnaire, available in English and Chinese. The data are transferred to the CKDOD database either by e-mail or via web access. All data are checked for consistency and missing values. Collection of data started in September 2011 and by April 2015, data on 1323 individual patients had been submitted. The mean age at inclusion was 57 ± 14 years, 67 % were male and 36 % were diabetic. The baseline estimated glomerular filtration rate was 26 ml/min/1.73 m(2). Of all enrolled patients, 324 (24 %) received ketoanalogue supplementation during at least one recorded visit. DISCUSSION: The CKDOD is a very large and comprehensive data repository, currently focused in subjects recruited from Asia. The database is expected to provide important long-term information on CKD progression, nutritional and metabolic derangements that accompany CKD progression and treatment strategies to ameliorate progression and complications of CKD. TRIAL REGISTRATION: Clinical Trial Registry - India: CTRI/2012/06/002743 ; 25th July 2012.

Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually. METHODS: We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected. RESULTS: The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18-98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively. CONCLUSION: The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.

What do we know about chronic kidney disease in India: first report of the Indian CKD registry.

BACKGROUND: There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics. METHODS: Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively. RESULTS: The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology. CONCLUSIONS: This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.

Monotherapy with peginterferon alpha-2b {12 kDa} for chronic hepatitis C infection in patients undergoing haemodialysis.

BACKGROUND: A combination of Peginterferon and Ribavirin is the standard treatment for patients with chronic hepatitis C viral infection (HCV). Ribavirin is contraindicated in patients with chronic renal failure (CRF). Conventional Interferon monotherapy is effective in around 30% of such patients. There is scanty data on the use of Peginterferon monotherapy in them. METHODS: We describe our preliminary experience of monotherapy with Peginterferon alpha- 2b {12 kDa} (Peg-IFN) for HCV patients undergoing haemodialysis for CRF. They were treated with Peg-IFN 1 microg/kg body weight subcutaneously once a week for 24 weeks. In all patients, clinical (age, sex, mode of acquiring HCV, pattern of haemodialysis) and virological (HCV RNA quantitative-PCR and genotype) profile was noted at baseline. Early virological response at 12 weeks (EVR), end-of-treatment virological response at 24 weeks (ETVR) and sustained virological response after 6 months of stopping treatment (SVR) were noted during the follow-up period. RESULTS: The clinical and virological characteristics of patients were as follows: Of a total number of 6 patients, 5 were male and 1 was female with an age range of 35 to 62 years. The duration of haemodialysis was from between 5 and 12 months before the start of treatment and its frequency lay between 1 and 3 times a week. The mode of acquiring HCV was blood transfusion (100%). All 6 cases suffered from chronic hepatitis. The genotype distribution was genotype 3 in 3 (50%), genotype 1 in 1 (16.7%) and genotype none of 6 in 2 (33.3%) patients. All the patients (100%) completed treatment. EVR was seen in all 6 patients (100%). ETVR was seen in 5 of 6 patients (83.3%). A follow-up period of more than 1 year was available in 4 patients. 3 of these 4 patients (75%) had SVR. A virological response was maintained in all 3 (100%) patients with SVR even after 6 months of renal transplantation. CONCLUSION: Peg-IFN monotherapy is safe and effective in patients with HCV who are on haemodialysis for CRF.

Tuberculosis in renal transplant recipients: rifampicin sparing treatment protocol.

The reactivation of mycobacterium infection in renal transplant recipients in developing countries is a common therapeutic dilemma, especially in those patients receiving cyclosporin immunosuppression. The inclusion of rifampicin in the antituberculosis protocol increases the risk of precipitating acute allograft rejection due to its interaction with cyclosporin and also increases the financial burden. We successfully treated 16 patients who developed mycobacterial infection post renal transplant with a rifampicin sparing antituberculosis drug regimen. Pyrexia of unknown origin was the most common manifestation observed and a therapeutic trial with antituberculosis drugs is justified. De novo diabetes mellitus appears to be an added risk factor and increases the susceptibility to mycobacterial infection.

Esophageal actinomycosis in a patient with end-stage renal disease.

Actinomycosis of esophagus is uncommon. Herpes simplex virus, cytomegalovirus, candidiasis, tuberculosis, and other fungal infections are the commonly reported infections in both immunocompromised and immunocompetent patients. We report a case of esophageal actinomycosis in an end-stage renal disease patient. A 28-year-old lady, known case of systemic lupus erythematosus, hepatitis B virus infection with end-stage renal disease on regular maintenance hemodialysis since 5 years presented with history of epigastric pain and odynophagia for 1 week. Her upper gastrointestinal endoscopic examination revealed extensive necrotic areas with membrane in the esophagus. Histopathology revealed actinomycotic colonies and bacterial clumps. She was treated with intravenous penicillin followed by oral ampicillin for 6 months. She showed marked clinical improvement, and repeat endoscopy showed healing of ulceration and no evidence of actinomycosis.

Severe pulmonary hypertension in a young patient with end-stage renal disease on chronic hemodialysis.

Severe pulmonary hypertension in a teenager with end-stage renal disease on chronic hemodialysis via arteriovenous access is reported. Clinical presentation included persistent volume overload and pericardial effusion. Serial hemodynamic data obtained at cardiac catheterization confirmed the diagnosis. In addition, detailed biochemical and imaging data (echo- Doppler, computed tomography of chest, computed tomographic pulmonary angiography, VQ lung scan, etc.) were obtained to find out the mechanism. The exact cause of pulmonary hypertension remains unclear, and a multi- factorial mechanism is postulated. This rare case is presented to highlight the role of aggressive dialysis, pericardiocentesis, and use of sildenafil and bosentan in the management.

Delivery of renal replacement therapy in acute kidney injury: what are the key issues?

BACKGROUND AND OBJECTIVES: The prescription and delivery of renal replacement therapy for acute kidney injury is subject to a wide variation and is conditioned by a multiplicity of factors. A variety of renal replacement therapy modalities are now available to treat acute kidney injury; however, there are no standards for the dosage, choice of modality, and intensity and duration of these therapies. Although several observational and interventional studies have addressed these topics, there are no consensus recommendations in this field. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The available literature on this topic and draft consensus recommendations for research studies in this area were developed using a modified Delphi approach and an international multidisciplinary network. RESULTS: The following questions were most important: What is the "dosage" of renal replacement therapy delivered to patients with stage 3 acute kidney injury? What is the optimal "dosage" of renal replacement therapy to maximize patient and renal survival? Is there a minimal "dosage" of renal replacement therapy required in patients with single-organ failure? Does modality of renal replacement therapy selected have an effect on patient and/or renal survival? In cases of continuous renal replacement therapy, does citrate anticoagulation confer a benefit? CONCLUSIONS: This report summarizes the available evidence and elaborates on the key questions and the methods that should be used so that the goal of standardizing the care of patients with acute kidney injury and improving outcomes can be achieved.