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.

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.

The Promise of Cilnidipine in Hypertension with Comorbidities: National Consensus Statement: National Consensus Group Comprises Cardiologists, Nephrologists, and Diabetologists from India in a National Meet at New Delhi held on 22nd May 2022.

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement.

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

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.

Multidisciplinary Consensus Document on the Management of Uncontrolled Hypertension in India.

Cardiovascular disease is predicted to be the largest cause of death and disability in India by 2020. Hypertension (HT), one of the main contributing factors, presents a significant public health burden. Inability to achieve adequate blood pressure (BP) control results in uncontrolled hypertension (UHT). The prevalence of UHT is high in India, with only about 9-20% of patients achieving target BP goals. Presently, there are no guidelines specific to UHT, which if left uncontrolled can lead to resistant HT, chronic kidney disease and other complications of HT. A multidisciplinary panel, comprising of specialists in cardiology, nephrology and internal medicine, was convened to address the diagnosis and management of UHT in the Indian population. The panel identified key points concerning UHT and discussed management recommendations in the Indian clinical setting.

Analgesic efficacy of two doses of intrathecal midazolam with bupivacaine in patients undergoing cesarean delivery.

OBJECTIVES: In this prospective, randomized, double-blind, placebo-controlled study, we investigated the postoperative analgesic efficacy of 2 doses of intrathecal midazolam as an adjunct to bupivacaine for spinal anesthesia. METHODS: Sixty patients undergoing elective cesarean delivery under spinal anesthesia were allocated randomly to 3 groups: group B, 2 mL hyperbaric bupivicaine 0.5%; group BM1, 2 mL bupivacaine plus midazolam 1 mg (preservative free); and group BM2, 2 mL bupivicaine plus midazolam 2 mg. RESULTS: The mean duration of postoperative analgesia (determined by request for rescue medication) was 3.8 +/- 0.5 hours in group B compared with 4.3 +/- 0.7 hours in group BM1 (P = .18), and 6.1 +/- 1.0 hours in group BM2 (P = .001). Supplemental analgesic requirements with diclofenac were significantly less in group BM2 (93 +/- 29 mg) compared with group B (145 +/- 12 mg) and group BM1 (148 +/- 16 mg, P < .001). Time to block regression was longer in group B (182 +/- 30 minutes) compared with group BM1 (152 +/- 32 minutes) and group B (126 +/- 20 minutes) (both P < .001). Arterial pressure, heart rate, oxygen saturation, sedation score, and time to first void were comparable between groups. Group B had a significantly higher incidence of nausea and vomiting than groups BM1 and BM2 (P = .02). No neurologic deficits were observed. CONCLUSIONS: Intrathecal midazolam 2 mg provided a moderate prolongation of postoperative analgesia when used as an adjunct to bupivacaine in patients undergoing cesarean delivery. Intrathecal midazolam, 1 mg and 2 mg, decreased postoperative nausea and vomiting.

Percutaneous reconstruction of chronic total occlusion of brachiocephalic vein using transseptal needle in dialysis-dependent patient.

Placement of a dialysis catheter substantially increases the risk of central vein stenosis. 52-year-old female with end-stage renal disease and a right brachial-cephalic hemodialysis access presented with right arm swelling. The chronic total occlusion of right brachiocephalic vein was refractory to wire traversal. Sharp recanalization of the central venous occlusion was done with transseptal needle retrogradely. The track was balloon dilated and stented. When the conventional catheters and guide wires options fail, sharp recanalization technique may be used to salvage a precious dialysis access.

Evaluation of Glycemic Control in Type 2 Diabetes Mellitus using Cytomorphometry of Buccal Cells and Correlation with Glycosylated Hemoglobin.

BACKGROUND: To study cytological alterations in the exfoliated buccal cells of diabetic patients. To analyze the cytomorphometric findings in the smears of uncontrolled and controlled diabetic patients and compare it with that of normal healthy controls. To establish a correlation between cytomorphometric changes and glycosylated hemoglobin (HbA1c) in diabetics and normal controls, for evaluation of glycemic control. MATERIALS AND METHODS: The study was carried out in 40 confirmed diabetic patients from a hospital out-patient diabetic ward and 20 healthy individuals as controls (Group A: n = 20), in Chennai. Specific exclusion criteria were used to select the study group from a larger group of subjects. Based on HbA1c values, the diabetic patients were categorized into Group B = Controlled diabetics (n = 20) (HbA1c <7%) and Group C = Uncontrolled diabetics (n = 20) (HbA1c >9%). After informed consent, buccal smear was collected from clinically normal appearing mucosa and stained with papanicoloau (PAP) stain. Cytomorphometric analysis of selective PAP stained cells was done using image analysis software, Image Pro Plus 5.5 (Olympus) and parameters determined were average cytoplasmic area (CA), average nuclear area (NA) and cytoplasmic:nuclear (C: N) ratio for an average of 50 cells/patient. RESULTS: Comparing the average NA among three groups, an increase through Group A, B, C, with a maximum significance between Group C and A was seen. The average C: N ratio showed a statistically significant difference between all three groups. Significant correlation existed between the HbA1c values and both the C: N ratio and average NA in all the three groups. CONCLUSIONS: Cytomorphometric analysis of buccal smears using the C: N ratio alteration as a reliable criteria, may serve as yet another non-invasive tool for screening programs for diabetic detection. And the technique may possibly be used also for evaluation of glycemic control in known diabetics.

Randomized, double-blind, placebo-controlled trial to evaluate efficacy of ketodiet in predialytic chronic renal failure.

OBJECTIVE: To assess whether a ketodiet, a combination of ketoanalogs of essential amino acids (KAs) and a very low-protein diet, retards progression of chronic renal failure and maintains nutritional status. DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: Nephrology outpatient department in Northern Railways Central Hospital, New Delhi, India. PATIENTS: Thirty-four patients in predialytic stages of chronic renal failure (CRF), randomized to 2 comparable groups in terms of age, sex distribution, blood pressure control, etiology, use of angiotensin converting enzyme inhibitors, serum creatinine, glomerular filtration rate (GFR), and body mass index (BMI). INTERVENTION: Subjects randomly received either 0.6 g/kg/d protein plus placebo (n = 16) or 0.3 g/kg/d protein plus tablets of KAs (Ketosteril; Fresenius Kabi, Germany) (n = 18) for 9 months. A dietician administered the diet as well as the KAs or the placebo to the patients. OUTCOME MEASURES: Changes in GFR and renal and nutritional parameters were measured. RESULTS: Mean (+/- SD) GFR measured by the 99mTc-DTPA (99 m technetium diethylenetri-aminepenta-aceticacid) plasma sample method was unchanged in the ketodiet group: 28.1 +/- 8.8 (before) and 27.6 +/- 10.1 mL/min/1.73 m2 (after the study) (P =.72). However, it significantly decreased from 28.6 +/- 17.6 to 22.5 +/- 15.9 mL/min/1.73 m2 in the placebo group (P =.015). Serum creatinine before and after the study in the ketodiet group was 2.26 +/- 1.03 mg/dL and 2.07 +/- 0.8 mg/dL (P =.90) and in the placebo group was 2.37 +/- 0.85 and 3.52 +/- 2.9 mg/dL (P =.066), respectively. In both groups the mean BMI did not change from 25.4 +/- 4.2 to 24.5 +/- 4.2 kg/m2 (P =.46) for ketodiet and from 25.0 +/- 6.8 to 23.9 +/- 4.1 kg/m2 (P =.39) for the placebo group. Serum total proteins decreased significantly (P =.038) in the placebo group, and serum albumin showed a trend (P =.061) toward reduction, whereas both of these parameters were maintained in the ketodiet group. CONCLUSION: Over a 9-month period, very low-protein diet supplemented with ketoanalogs helped CRF patients to preserve GFR and maintain BMI. KAs were safe and efficacious in retarding the progression of renal failure and preserving the nutritional status of CRF patients.

Effects of correction of metabolic acidosis on blood urea and bone metabolism in patients with mild to moderate chronic kidney disease: a prospective randomized single blind controlled trial.

BACKGROUND: There are no controlled trials on the efficacy of oral bicarbonate therapy in patients with mild to moderate chronic kidney disease (CKD). This prospective randomized controlled study was done to evaluate the effects of correction of metabolic acidosis on renal functions and bone metabolism in this group of patients. PATIENTS AND METHODS: Forty patients were randomized to treatment with oral bicarbonate or placebo for a period of 3 months. Investigations at baseline included venous pH, bicarbonate, renal functions, serum iPTH, and bone radiology. The treatment group (Group B) received daily oral sodium bicarbonate therapy at a dose of 1.2 mEq/kg of body weight. Their venous blood pH and bicarbonate levels were estimated weekly to keep blood pH near 7.36 and bicarbonate at 22-26 mEq/L by adjusting the dose of sodium bicarbonate. At the end of 3 months, all the tests were repeated in both groups. RESULTS: After oral bicarbonate therapy (OBT), there was a significant decline in the rise of blood urea level in Group B associated with a sense of well-being in 50% patients. The rise in parathormone (PTH) was six times the baseline value in Group A and only 1.5 times baseline value in Group B, although not statistically significant. There was no significant change in total calcium, phosphorus, alkaline phosphatase, creatinine, total protein, or albumin levels. CONCLUSION: Correction of metabolic acidosis in patients with moderate CKD attenuates the rise in blood urea and PTH, which might prevent the deleterious long-term consequences of secondary hyperparathyroidism.

Autosomal dominant progressive nephropathy with deafness: linkage to a new locus on chromosome 11q24.

Focal segmental glomerulosclerosis (FSGS) and Alport syndrome (AS) are two major causes of end-stage renal disease (ESRD). A few families with autosomal dominant FSGS have been reported with linkage to chromosome 19q13 or 11q22, while AS is usually linked to mutations in type IV collagen (COL4) subunit genes. A phenotype resembling AS may also be seen with myosin heavy chain-9 (MYH9) gene mutations. This study ascertained a multigeneration family (CHP-177) with clinical aspects of both FSGS and AS where we identified a new locus for the trait. A genome-wide scan was performed with 400 markers, and fine mapping was performed for chromosome 11 markers. Data were analyzed by GENEHUNTER and VITESSE under various models. CHP-177 is a 39-member kindred residing near New Delhi, India, with seven affecteds and showed male-to-male transmission. Two members had ESRD. Renal biopsies showed both FSGS lesions and thin glomerular basement membranes. Five of the affecteds also had sensorineural deafness, which involved both low and high frequency in some members. The AS loci, i.e., COL4A3/COL4A4 and MYH9 (LOD scores: -6.1 and -4.3, respectively) and FSGS loci, on 19q13 and 11q22, were excluded from linkage. A significant evidence of linkage was observed for 11q24 region, with a multipoint LOD (z-score) of 3.2 for marker D11S4464 at theta = 0. The z-1 confidence interval for the linked region spans a genetic distance of 7 cM. This study thus reports an autosomal dominant nephropathy with features of both FSGS and AS in which linkage to currently known loci for such phenotypes was excluded and a new locus on 11q24 was identified. The findings suggest further locus heterogeneity for the autosomal dominant nephropathy phenotype.