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.

Clinicopathologic Spectrum and Outcomes of Infections Diagnosed on Graft Biopsies and Nephrectomy in Live Renal Allograft Recipients: An Institutional Experience.

OBJECTIVES: Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens. MATERIALS AND METHODS: Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records. RESULTS: BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis. CONCLUSIONS: BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.

ABO-Incompatible Renal Transplant: A Single-Center Experience from India.

Introduction: In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. Methods: Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks. Results: A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients. Conclusion: ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

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 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.

Observation of negative terahertz photoconductivity in strongly correlated electron-doped CaMnO3thin film.

Electron-doped Ca0.96Ce0.04MnO3(CCMO) possesses a unique band structure and exhibits a giant topological Hall effect contrary to other correlation-driven manganites known for insulator-to-metal transition, magnetoresistance, complex magnetic order, etc. The interaction mechanisms among the fundamental entities and their dynamical evolutions responsible for this unusual topological phase are yet to be understood. Here, we employ time-averaged and sub-picosecond time-resolved terahertz (THz) spectroscopy to explore the low-energy steady-state and ultrafast carrier dynamics, respectively, to unravel the complexity of charge carriers during their transition from a non-equilibrium state to the ground state in CCMO thin film. The THz optical conductivity confirms the presence of dichotomic charge carriers, i.e. heavy and light carriers throughout the temperature range of 15-300 K. A rare observation of both positive and negative photoconductivities along with a sharp crossover between the two resolved to a few picoseconds of illumination confirms the formation of polaron with a lifetime of a few nanoseconds. These optical evidences of dichotomic charge carriers, along with manipulation of the sign of photoconductivity induced by dynamics of related quasiparticles could facilitate a new mechanism for ultrafast optoelectronic switching devices.

High-value crops' embedded groundnut-based production systems vis-à-vis system-mode integrated nutrient management: long-term impacts on system productivity, system profitability, and soil bio-fertility indicators in semi-arid climate.

The current study identified two new climate-resilient groundnut-based cropping systems (GBCSs), viz., groundnut-fenugreek cropping system (GFCS) and groundnut-marigold cropping system (GMCS), with appropriate system-mode bio-compost embedded nutrient management schedules (SBINMSs) for semi-arid South Asia. This 5-year field study revealed that the GMCS along with leaf compost (LC) + 50% recommended dose of fertilizers (RDF50) in wet-season crop (groundnut) and 100% RDF (RDF100) in winter-season crop (marigold) exhibited the highest system productivity (5.13-5.99 t/ha), system profits (US$ 1,767-2,688/ha), and soil fertility (available NPK). Among SBINMSs, the application of 5 t/ha leaf and cow dung mixture compost (LCMC) with RDF50 showed the highest increase (0.41%) in soil organic carbon (SOC) followed by LC at 5 t/ha with RDF50 and RDF100. Legume-legume rotation (GFCS) had significantly higher soil microbial biomass carbon (SMBC) and soil microbial biomass nitrogen (SMBN) than legume-non-legume rotations (groundnut-wheat cropping system (GWCS) and GMCS). Among SBINMSs, the highest SMBC (201 µg/g dry soil) and SMBN (27.9 µg/g dry soil) were obtained when LCMC+RDF50 was applied to groundnut. The SMBC : SMBN ratio was the highest in the GWCS. LC+RDF50 exhibited the highest SMBC : SOC ratio (51.6). The largest increase in soil enzymatic activities was observed under LCMC+RDF50. Overall, the GMCS with LC+RDF50 in the wet season and RDF100 in the winter season proved highly productive and remunerative with better soil bio-fertility. SBINMSs saved chemical fertilizers by ~25%' in addition to enhanced system productivity and system profits across GBCSs in semi-arid regions of South Asia. Future research needs to focus on studying the potential of diversified production systems on water and environmental footprints, carbon dynamics, and energy productivity under semi-arid ecologies.

Clinicopathological investigation of nutritional osteodystrophia fibrosa in a flock of young stall-fed goats.

Background: Osteodystrophia fibrosa (ODF) is a metabolic disorder affecting the skeletal system, causing progressive loss of calcified bone mass and its replacement with fibrous tissue, which may be a sequel to primary or secondary hyperparathyroidism. This report intends to document the clinicopathological findings of ODF in a flock of young goats fed primarily on a wheat bran-rich diet. Case description: In a flock of 50 stall-fed goats aged 1 to 2 years, seven were clinically presented with bilateral facial enlargement, leading to dyspnea and difficulty in prehension and mastication. Among the seven clinically affected goats, four died in 2 months. Findings/treatment and outcome: The clinical examination revealed bilateral mandibular enlargement and limb deformities. On radiography, the maxilla and mandible had decreased radiopacity. Fine needle aspiration cytology (FNAC) from the affected bones showed occasional fibroblasts and individual osteoclasts clusters. On necropsy, the enlarged mandible revealed a meaty consistency. Undecalcified histological sections of the mandible showed severe osteopenia, multiple osteoclasts, Howship's lacunae, and extensive fibroplasia. Dietary corrective measures led to the prevention of ODF in the rest of the flock. Conclusion: Excessive wheat bran feeding in stallfed goats might have led to calcium and phosphorus imbalance, resulting in nutritional secondary hyperparathyroidism and subsequent skeletal deformities. FNAC of the affected bones, gross and histological findings provide a clinicopathological diagnosis of ODF.

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.

Anti-T-Lymphocyte Immunoglobulin (Grafalon) as an Induction Agent for Renal Transplantation: A Real-World, Retrospective, Single-Center Experience.

OBJECTIVES: Polyclonal antithymocyte globulins are widely used in the induction regimens of solid-organ transplant recipients; however, their doses and outcomes remain to be standardized in Indian patients. We report our clinical experience from the real-world use of Grafalon (an anti-T-lymphocyte globulin; ATG-Fresenius) as an induction agentin renal transplant recipients from India. MATERIALS AND METHODS: In this retrospective, single- center, observational study, we analyzed the medical records of 177 consecutive, kidney-only transplant recipients who received induction therapy with Grafalon from September 2016 to March 2018 at our center. Incidences of biopsy-proven acute rejection and graft dysfunction, immunosuppression protocol, Grafalon dosage, 18-month post-transplant graft and patient survival, treatment-related adverse events, and infective complications were reported. RESULTS: Mean age of patients was 41.46 years (range, 14-68 years), (85% were males). The average dose of Grafalon was 5.81 ± 1.95 mg/kg (range, 2.41 to 10.07 mg/kg). Graft dysfunction (ie, at least 20% increase in serum creatinine from baseline) was observed in 26 patients (14%): 11 patients (6.2%) had biopsy-proven acute rejections, 11 patients (6.2%) had acute tubular necrosis, and 4 patients (2.2%) had calcineurin inhibitor toxicity. Seven deaths were recorded: 2 each from fungal pneumonia, bacterial pneumonia, and acute coronary syndrome and 1 with urinary tract infection with septicemia. Death-censored graft survival was 100% at 12 months and 98% at 18-month follow-up; overall patient survival was 96%. Infective complications occurred in 40 patients (22.5%), with the most common being urinary tract infection in 32 patients (18%). No malignancies were reported. CONCLUSIONS: Use of a potent induction therapy like anti-T-lymphocyte globulin (Grafalon) is often restricted by the risk of side effects and lack of local clinical evidence supporting its role in long-term graft survival. Real-world evidence support the safe and effective use of anti-T-lymphocyte globulin as an induction agent in renal transplant recipients with an individualized dosing approach.

Hypervitaminosis D and Acute Interstitial Nephritis: Tale of Injections.

A 33-year-old man came with nausea, vomiting and abdominal pain due to hypercalcaemia and renal dysfunction following two doses of intramuscular vitamin D injections. Levels of vitamin D were repeatedly above 300 ng/ml over a period of 10 months. Whole-body PET CT scan revealed a thin-walled collection in the right gluteal region. The patient refused a surgical intervention for the same. After 7 months of follow-up, the abscess ruptured spontaneously and was then surgically debrided. At this point, a history of pentazocine addiction was uncovered. One month later, vitamin D levels began to fall along with improvement in serum calcium and creatinine. This case unravels a diagnostic odyssey which ended with a simple surgical debridement. We aim to highlight that vitamin D supplementation in 'megadoses' in the presence of active infection can have an exaggerated response and may take months to resolve.

Post-transplant Lymphoproliferative Disorder Presenting as Breast Nodule and Intestinal Obstruction in a Renal Transplant Recipient: A Case Report.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication among kidney transplant recipients. The clinical presentation of patients with PTLD is highly variable. The type of PTLD and the area of involvement determine its presentation, which includes constitutional symptoms such as fever, weight loss, fatigue, and other symptoms related to dysfunction of involved organs, or compression of surrounding structures. Most present with extranodal masses involving the gastrointestinal tract (stomach, intestine), lungs, skin, liver, central nervous system, and the allograft itself. In our case, a 33-year-old woman developed Epstein-Barr virus-negative PTLD plasmablastic lymphoma (PbL) in her right breast and small intestine presenting as intestinal obstruction, 15 years after renal transplant. Her condition was managed with intestinal mass resection and chemotherapy. A follow-up positron emission tomography scan showed near-complete resolution. Thus, PTLD should always be kept in mind in renal transplant recipients who present with features of a mass effect involving any organ.

Double whammy: anticoagulant-related nephropathy with leukocytoclastic vasculitis due to warfarin.

Anticoagulation-related nephropathy (ARN) is a rare form of acute kidney injury where the use of anticoagulation causes hemorrhage in various compartments of nephron including glomerulus, renal tubules, and interstitial compartment. Also, warfarin-induced vasculitis is an extremely rare condition characterized by the appearance of purpuric lesions on the skin which on biopsy are suggestive of leukocytoclastic vasculitis (LV). We hereby report a case presenting with coexistent warfarin-induced nephropathy and cutaneous vasculitis. A 64-year-old male, on warfarin for 10 years, presented with complaints of palpable purpuric rashes over lower limbs, hematuria, and decrease urine output. INR was in the supratherapeutic range (INR-6.3). Skin biopsy of the lesion was suggestive of LV and kidney biopsy showed RBCs in Bowman's capsule, RBCs and RBC casts in tubules suggestive of ARN. All vasculitic markers were negative. Thus, a diagnosis of warfarin-induced nephropathy and cutaneous vasculitis was made. Warfarin was discontinued and oral steroids were started. Gradually, his skin lesions improved, and he became dialysis independent. He was then discharged on apixaban. On follow-up after 3 months, his skin lesions had disappeared with partial recovery of kidney function (cr-5.49).

Interventional nephrology and vascular access practice: A perspective from South and Southeast Asia.

South and Southeast Asia is the most populated, heterogeneous part of the world. The Association of Vascular Access and InTerventionAl Renal physicians (AVATAR Foundation), India, gathered trends on epidemiology and Interventional Nephrology (IN) for this region. The countries were divided as upper-middle- and higher-income countries as Group-1 and lower and lower-middle-income countries as Group-2. Forty-three percent and 70% patients in the Group 1 and 2 countries had unplanned hemodialysis (HD) initiation. Among the incident HD patients, the dominant Vascular Access (VA) was non-tunneled central catheter (non-TCC) in 70% of Group 2 and tunneled central catheter (TCC) in 32.5% in Group 1 countries. Arterio-Venous Fistula (AVF) in the incident HD patients was observed in 24.5% and 35% of patients in Group-2 and Group-1, respectively. Eight percent and 68.7% of the prevalent HD patients in Group-2 and Group-1 received HD through an AVF respectively. Nephrologists performing any IN procedure were 90% and 60% in Group-2 and Group 1, respectively. The common procedures performed by nephrologists include renal biopsy (93.3%), peritoneal dialysis (PD) catheter insertion (80%), TCC (66.7%) and non-TCC (100%). Constraints for IN include lack of time (73.3%), lack of back-up (40%), lack of training (73.3%), economic issues (33.3%), medico-legal problems (46.6%), no incentive (20%), other interests (46.6%) and institution not supportive (26%). Routine VA surveillance is performed in 12.5% and 83.3% of Group-2 and Group-1, respectively. To conclude, non-TCC and TCC are the most common vascular access in incident HD patients in Group-2 and Group-1, respectively. Lack of training, back-up support and economic constraints were main constraints for IN growth in Group-2 countries.

Chylous Ascites after Laparoscopic Donor Nephrectomy: Case Report.

Chylous ascites refers to the accumulation of chyle in the abdominal cavity. Postoperative chylous ascites is most commonly associated with abdominal aortic surgeries. However, it is a rare complication following laparoscopic nephrectomy. It causes loss of fat, protein, and antibodies causing malnutrition and immunodeficiency. Thus, it is important to treat it as early as possible. We hereby report a case of chylous ascites following laparoscopic donor nephrectomy. A 55-year-old female was admitted at our center 2 weeks after undergoing left laparoscopic donor nephrectomy with abdominal distension and constipation. USG abdomen revealed free fluid in the abdomen. Paracentesis revealed chylous ascites. The patient was started on conservative treatment, including a diet rich in proteins and low in fats; conservative treatment, however, was unsuccessful. Lymphangiography and subsequent embolization of the defect were done, and she made a full recovery.

Crop and water productivity, energy auditing, carbon footprints and soil health indicators of Bt-cotton transplanting led system intensification.

Direct-seeded-cotton (DSC) leads to low crop and water productivity and energy-output with higher carbon-footprints besides impairing system-intensification under conventional cotton-wheat cropping system (CWCS). Hence, we evaluated two methods of Bt-cotton establishment [transplanted cotton (TPC) & DSC)] at three planting geometries/densities in four Bt-cotton based cropping-systems [DSC-wheat (DSC-W), TPC-wheat-mungbean (TPC-W-M), DSC-onion (DSC-O), TPC-onion-fodder cowpea + fodder maize (TPC-O-FC + FM)] in semi-arid region of south Asia. Poly-glass nursery-raised TPC exhibited significantly higher germination (96.5%), seedling-survival (96.1%) and 14.1% higher plant-stand owing to lower seedling-mortality (3.2%). TPC used ∼60% less irrigation-water but exhibited significantly higher seed-cotton, seed and lint yield, net-returns, radiation-use-efficiency and water-productivity by 11.4, 9.9, 14.3, 17.3, 10.7 and 260.6%, respectively over DSC. Planting geometry/density of 60 × 45 cm (37,037 plants ha-1) exhibited significantly higher crop and water productivity and economic-returns. Bt-cotton transplanting led system-intensification enhanced the system-productivity (26.1%), profitability (30.5%), water-productivity (19.3%) and land-use-efficiency (8.5%) over the DSC-based systems with significantly higher values under TPC-O-FC + FM. Energy-use pattern reveled that farm inputs viz. Fertilizers (54-60%), water (15-25%) and diesel (6-10%) consumed bulk of the input-energy in different cropping systems with greatest values under TPC-O-FC + FM. TPC-W-M exhibited highest system energy-output (604.6 × 103 MJ ha-1) and energy-returns (566.2 × 103 MJ ha-1). TPC-O-FC + FM exhibited significantly higher carbon-consumption (668.9 kg CE ha-1) and carbon-output (21431.3 kg CE ha-1) while maintaining significantly higher carbon-efficiency (32.0) and carbon sustainability index (31.0). TPC-O-FC + FM had least carbon-footprints (0.07 kg CE kg-1 SCEY) while conventional-CWCS exhibited 2-folds higher carbon-footprints. Legume-imbedded TPC-based cropping systems markedly increased the soil physical (bulk-density, water-stable-aggregates), chemical (SOC, available-NPK) and biological properties (soil-microbial-biomass-carbon, dehydrogenase and ergosterol activity) over the conventional CWCS and DCS-O systems. Overall, Bt-cotton transplanting led system-intensification upholds great importance in enhancing the system crop and water-productivity, profitability, energy-productivity, resource-use-efficiency and soil-health with minimal carbon-footprints in semi-arid agro-ecosystems of south Asia.