Acute Airway Obstruction: An Unusual Presentation of Posttransplant Lymphoproliferative Disorder in a Renal Transplant Recipient.

Posttransplant lymphoproliferative disorder is a life-threatening complication after solid-organ transplants. In adults, recipients of heart transplants have the highest risk, whereas renal transplant recipients have the lowest risk among all solid-organ transplants. The most common site for posttransplant lymphoproliferative disorders are gastrointestinal tract followed by the graft itself. Airway involvement in posttransplant lymphoproliferative disorder is rarely encountered. We report a case of a 26-year-old renal allograft recipient who presented to the emergency room with airway obstruction necessitating an emergency tracheostomy. Imaging revealed a left tonsillar mass extending into the nasopharynx and retropharyngeal space causing complete oropharyngeal occlusion. Endoscopic biopsy from nasopharyngeal mass showed a diffuse large B-cell lymphoma and was Ebstein-Barr virus positive. Reduction in immunosuppression and treatment with posttransplant lymphoproliferative disorder-1 risk-stratified approach resulted in complete remission.

Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.

OBJECTIVE: To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. DESIGN: CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. SETTING: 17 hospital sites in India and Australia. PARTICIPANTS: Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. INTERVENTION: Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. MAIN OUTCOME MEASURES: The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. RESULTS: Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. CONCLUSIONS: In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. TRIAL REGISTRATION: ClinicalTrials.gov NCT04394117.

Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go.

Chronic kidney disease (CKD) not associated with known risk factors has been reported from parts of India and is presumed to be similar to CKD of unknown etiology (CKDu) that has been described from Central America. The reports from India have been fragmented without clear description of the disease phenotype or its determinants. This paper summarizes the current state of knowledge around CKDu in India based on a review of literature, multi-stakeholder consultation, and a survey of Indian nephrologists. We also contacted individual research groups to solicit data. Our findings suggest that that CKDu is reported from most regions in India; however, it is interpreted differently from the phenotype described from Central America and Sri Lanka. The differences include lack of a clear demographic or occupation group, older age of affected participants, and presence of mild hypertension and low-grade proteinuria. Well-designed prospective field studies with appropriate diagnostic workup are needed to establish the disease burden and identify etiologies, along with socioeconomic and health consequences, the intersection with the environment, and the public health response. Community-based research should phenotype the entire CKD population rather than be restricted to cases with presumed CKDu based on predefined criteria. Guidelines are needed for clinical evaluation, referral, management, and harmonization of clinical documentation and health records. More data are needed to support the existence of a unique CKDu phenotype in India.

Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial.

BACKGROUND: SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes. METHODS AND DISCUSSION: CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).

Membranoproliferative glomerulonephritis: A rare presentation of occult filariasis.

Parasitic infections do not usually present with rapidly progressive renal failure but can provoke glomerular lesions which are mostly proliferative. In filarial infection, glomerular involvement is usually mild and transient, and presentation with renal failure is rare. We report occult filariasis presenting as rapidly progressive renal failure due to immune-complex mediated membranoproliferative glomerulonephritis. Our patient responded to treatment with diethylcarbamazine and a short course of steroid. This case highlights the importance of thorough workup to identify the cause and consideration of filariasis in an endemic area.

Extending the ambit of SGLT2 inhibitors beyond diabetes: a review of clinical and preclinical studies on non-diabetic kidney disease.

INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel antidiabetic agents with overwhelming cardiorenal protection. Recent trials focusing on the nephroprotective role of SGLT2i have underscored its success as a phenomenal agent in halting the progression of kidney disease in patients with and without Type 2 diabetes mellitus. Multitudes of pleiotropic effects on tubules have raised hopes for reasonable nephroprotection beyond the purview of the hyperglycemic milieu. AREA COVERED: This review summarizes various animal and human data as evidence for the utility of SGLT2i in non-diabetic chronic kidney disease (CKD). Web-based medical database entries were searched. On the premise of existing evidence, we have discussed mechanisms likely contributing to nephroprotection by SGLT2i in patients with non-diabetic CKD. EXPERT OPINION: Further elucidation of mechanisms of nephroprotection offered by SGLT2i is required to extend its use as a nephroprotective agent. The use of non-traditional markers of kidney damage in future studies would improve the evaluation of their role in attenuating CKD progression. Emerging animal data support the early use of SGLT2i in states of modest proteinuria for superior outcomes. Future long-term trials in patients should aim to address the time of intervention with SGLT2i during the natural disease course of CKD for best outcomes.

Severe Pancytopenia Following Single Dose Methotrexate In Psoriasis: A Rare And Potentially Lethal Manifestation.

Methotrexate is an anti-metabolite, anti-cancer drug frequently used in the treatment of extensive chronic plaque psoriasis. Psoriatic plaque erosion is a rare toxic side effect of single-dose methotrexate and is described as a sign of impending pancytopenia. Here, we report a case of a 48- year-old male presented with multiple oral and genital erosions, accompanied by fissuring over palm and soles for 5 days. His laboratory tests revealed severe pancytopenia and nephropathy. He had a history of chronic plaque psoriasis for which he took a single dose of 15 mg methotrexate. During the hospital stay, the patient needed folate antagonist, granulocyte colony-stimulating factor (G-CSF), intravenous fluids, blood transfusions, and platelet transfusions. He recovered within 12 days of admission.

Chronic kidney diseases: A realm for preventive nephrology.

Chronic Kidney Disease (CKD) is emerging as a major public health priority worldwide. It is a chronic condition influenced by lifestyle and behavior. The risk factors for CKD are highly prevalent among the Indian population, and the number of Indians at risk is increasing. Preventive measures focusing on reducing the prevalence of CKD by limiting exposure to risk factors could be cost effective in a country like India. Kidney diseases disproportionally affect disadvantaged populations and reduce the number of productive years of life. Furthermore, the prospect of financial burden discourages many patients from undergoing treatment, thereby leading to preventable morbidity and death. The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. Health literacy and self-management are critical to improving the outcomes of chronic conditions such as chronic kidney disease. Primary Care and Family physicians act as a bridge between the nephrologist specialist and the CKD patients; which will help in improving the quality of life, reduce physical and psychologic limitations and complications associated with CRF, and help patients return to their families, jobs, and social lives.

COVID-19 Pandemic and Children: A Review.

The severe respiratory disease COVID-19 (coronavirus disease 2019) was first reported in late December 2019 in Wuhan City, China. Soon thereafter, the World Health Organization (WHO) officially declared it a pandemic. The adult population is highly affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); however, infants and children are also not spared. Transmission in the pediatric population appears to be primarily from COVID-19-positive adults, largely from family contacts through droplets, direct contacts, and aerosols. There is also evidence of fecal-oral route of transmission. The incubation period of COVID-19 in children ranges from 2 to 10 days. Most children are asymptomatic. The most common symptoms amongst symptomatic children are fever and cough. Shortness of breath, sore throat, rhinorrhea, conjunctivitis, fatigue, and headache are other common symptoms. Diarrhea, vomiting, and abdominal pain are the common gastrointestinal symptoms that may be present with or without respiratory symptoms. Very few children are likely to develop severe disease.Supportive care is the mainstay of treatment. Though data are limited, antiviral therapies such as remdesivir, favipiravir, lopinavir/ritonavir, and other drugs like hydroxychloroquine/chloroquine have been used for severe COVID-19 cases, with remdesivir showing the greatest promise. A few children may develop an exaggerated immune response, characterized by exaggerated cytokine release and manifests with features similar to Kawasaki disease. The syndrome has been referred to by many names including pediatric inflammatory multisystem syndrome (PIMS) and more recently, as multisystem inflammatory syndrome in children (MIS-C); this life-threatening condition often requires a multidisciplinary team effort and use of immunomodulators.

Sofosbuvir-Velpatasvir Fixed Drug Combination for the Treatment of Chronic Hepatitis C Infection in Patients With End-Stage Renal Disease and Kidney Transplantation.

INTRODUCTION: India is witnessing high hepatitis C virus (HCV) infection burden in patients of chronic kidney disease. Due to unavailability of costly Kidney Disease Improving Global Outcomes-recommended directly acting antiviral drugs, a widely available pan-genotypic combination of Sofosbuvir and Velpatasvir can become an economical option. Data regarding treatment experience of sofosbuvir-velpatasvir combination in chronic kidney disease is scarce. No data from India have been published in patients on renal replacement therapies till now. METHODS: This retrospective analysis included all patients of end-stage renal disease on maintenance hemodialysis with treatment-naïve chronic HCV infection treated with sofosbuvir (400 mg) and velpatasvir (100 mg) fixed-dose combination. Pretreatment routine investigations were performed, which included HCV viral load, genotype, fibro scan, endoscopy for esophageal varices, and portal vein Doppler. The patients were followed up with HCV viral load to declare sustained virologic response. RESULT: patients were included with a mean age of 39.8 ± 10.8 years, and 77.4% were male. Genotype 1 was found to be most prevalent (67.7%), with a median viral load of 106copies/ml. Six (19.3%) patients had hepatitis B virus co-infection. Three (9.7%) patients had cirrhosis. Sustained virologic response (SVR12) was achieved in 30 (96.8%) patients, and one (3.2%) patient had relapse. Furthermore, 14 (45.2%) patients underwent renal transplantation, and none of them had relapsed. Dyspepsia (9.7%) was the most common side effect observed with no major adverse effect. CONCLUSION: Our study showed excellent efficacy with the safety profile of this drug combination in end-stage renal disease patients. However, larger prospective studies and multicenter randomized controlled trials are needed for further confirmation.

Chylothorax in a Child with Nephrotic Syndrome.

Chylothorax is an uncommon presentation of venous thrombosis in nephrotic syndrome. We present a case of an 8-year-old boy with nephrotic syndrome who presented with prolonged respiratory difficulty and dry cough. A detailed evaluation revealed left chylothorax secondary to thrombosis of the left brachiocephalic vein. He improved with conservative management including anticoagulation therapy, intercostal chest tube drainage, and dietary modification. This case highlights the need to consider venous thrombosis as a cause of chylothorax in patients with nephrotic syndrome to institute appropriate treatment.

Comparison between two different successful approaches to COVID-19 pandemic in India (Dharavi versus Kerala).

Various factors interplay when it comes to successful containment of pandemic. In last one year, we have witnessed various countries formulating and practicing their own unique ways to tackle coronavirus. We have seen the most developed countries failing terribly and unable to slow the COVID-19 spread, but at the same time also endorsed the comparatively less resourceful countries outperforming in terms of reduced disease morbidity and mortality. Current review is about two regions from India (Dharavi and Kerala) who were different in their approach as compared to rest of the country and were able to keep the COVID-19 cases to the minimum.

Chylous ascites during peritoneal dialysisin a toddler: a rare complication.

Chylous ascites is a rare complication of peritoneal dialysis (PD) and is often mistaken for peritonitis. It usually resolves following conservative management and does not pose any risk to the dialysis procedure. We report the case of a 2-year-old boy, who developed chylous ascites at 36 hours of PD and spontaneously resolved within the next 48 hours.