Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: a retrospective cohort study with follow-up from Mumbai, India.

BACKGROUND: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. METHOD: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. RESULTS: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation. CONCLUSION: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Anemia management in dialysis patients: a PIVOT and a new path?

PURPOSE OF REVIEW: We will examine the current and future options in management of anemia in dialysis patients focusing on recent trials in iron supplementation and alternatives to erythropoietin-stimulating agents (ESAs). RECENT FINDINGS: We review the literature on Erythropoietin (EPO)-stimulating agents, focusing on the risk benefits of various options available. We review the recent practice changing trial in iron supplementation in dialysis patients with chronic kidney disease and movements in the research on alternatives to EPO-stimulating agents primarily hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). SUMMARY: ESAs constitute the mainstay of treatment of anemia in dialysis and evidence does not support the preference of any one type over the other. But concerns exist about the cardiovascular safety of supra-physiological ESA levels. Iron supplementation has been shown to be a well tolerated method to decrease ESA doses while maintaining hemoglobin levels and recent evidence should result in a revisiting of the guidelines for iron supplementation. HIF-PHIs are potentially safe alternatives to ESAs that correct and maintain hemoglobin while maintaining physiological levels of erythropoietin. Ongoing phase III trials for these drugs will likely answer questions of long-term safety regarding these drugs.

Impact of COVID-19 on maintenance haemodialysis patients: The Indian scenario.

There is a lack of data describing the impact of the novel coronavirus 19 pandemic on the patients of chronic kidney disease stage V-dialysis (CKD V-D) from resource-limited countries. A growing body of literature describes an increased susceptibility of CKD V-D to COVID-19 with adverse outcomes in those with severe disease. In the current retrospective report, we elucidate the outcome in consecutive 37 CKD V-D patients with COVID-19 from two dialysis centres in Mumbai, India. Of the 37 patients included in the study, 56.7% of patients were asymptomatic or had mild disease and 27% presented with severe symptoms. The recovery rate was 63%, all those who presented with a severe disease succumbed to the infection. Thirty per cent of patients presented with an extended dialysis break due to various logistic and social issues. Though the overall clinical presentation and outcomes of this cohort from a limited resource setting mimic the global scenario, unique social and logistic issues are an additional burden to the patient, caregivers and the health-care facilities, which may worsen the outcomes in the future as the pandemic continues to spread.

Tip variant of focal segmental glomerulosclerosis: is it truly a benign variant?

BACKGROUND: Even though frequently described as a benign entity, the outcomes of the tip variant of focal segmental glomerulosclerosis (FSGS) have proven to be unclear. METHODS: This retrospective study includes a cohort of tip variant cases who presented to us from 2009 to 2012 and the analysis of their presenting clinical, histopathological features and treatment outcomes in comparison to the not otherwise specified (NOS) variants from our center in East India. RESULTS: Of the 224 biopsies of primary FSGS, 30 cases were the tip variant (13.39%). The mean age of presentation was around 29 years, with 57% being males. A nephrotic presentation was seen in 87% of cases, with 20% showing a presentation at <18 years of age for the first time. Global sclerosis, interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were seen more commonly in the NOS variant. Twenty five patients of tip variant received steroid therapy and eight received alternative immunosuppression. Around 87% of the tip variant cases achieved some form of remission in proteinuria and 13.3% had a doubling of creatinine at a median follow-up of 2 years in comparison to NOS group in which 80% achieved some form of remission and 20% had a doubling of creatinine. CONCLUSION: Though the histopathological features and treatment responsiveness of the tip variant appear to be better than the NOS variety, the prognostic outcome does not seem to be as favorable as implicated previously with an important percentage of patients showing progressive worsening of renal function within a relatively short time span (2 years) in our cohort.

Safety and feasibility of outpatient percutaneous native kidney biopsy in the developing world: experience in a large tertiary care centre in Eastern India.

AIM: Optimal time of observation following percutaneous biopsy has not been clearly established. Outpatient biopsy protocol was established in our centre for low risk patients and we assessed its efficacy and safety. METHODS: Patients fulfilling the low risk profile underwent a real time ultrasound-guided percutaneous native kidney biopsy. They were observed for 6 h and any complication was recorded. Ultrasound and hematocrit was done only in those patients with complications. Patients were contacted on telephone after 24 h and in case of any emergency. RESULTS: A total of 403 native kidney biopsies were performed from June 2011 to June 2012 of which 115 (28.5%) were on an outpatient basis. This was a 41.4% increase in the number of biopsies compared to the same period in the previous year. Fifteen patients (13.04%) had macroscopic haematuria within 2, 4 and 6 h in eight (53.33%), six (40%) and one (6.67%) patient, respectively. One of them had haematuria on follow-up phone call resolving without intervention. Only two (1.74%) patients developed significant bleeding with a drop in haematocrit needing overnight observation, with one requiring blood transfusion (with perinephric haematoma not requiring intervention). Complication rates were also similar in the 288 patients who had at least an overnight inpatient observation post-biopsy. There was no biopsy related mortality. CONCLUSIONS: Percutaneous native kidney biopsies can be safely performed on an outpatient basis in selected low risk patients. This approach increases the number of procedures, decreases the waiting periods and can have potential cost savings making it an attractive option in the developing world.

Spectrum of nephrotic syndrome in adults: clinicopathological study from a single center in India.

BACKGROUND: The etiology of nephrotic syndrome (NS) in adults varies depending on the geographical location and is poorly studied in the Indian subcontinent. METHODS: Patients (≥16 years old) with NS presenting to our center and undergoing a kidney biopsy from April 2010 to September 2012 were included for this study. All biopsies were subjected to light and immunofluorescence microscopy, and electron microscopy in selected cases. The histopathological spectrum was analyzed according to the various clinical parameters. RESULTS: A total of 410 kidney biopsies were included for analysis. Two hundred and thirty seven (57.8%) patients were male and 173 (42.19%) patients were female. The average age at presentation was 33.68 ± 13.88 years. Among the patients, 88.05% (n = 361) were diagnosed with primary glomerular diseases (PGD) and 11.95% (n = 49) with secondary glomerular diseases (SGD). The most common histological lesions were focal segmental glomerulosclerosis (FSGS) (24.63%) followed by minimal change disease (MCD) (23.9%) and membranous nephropathy (MN) (22.44%). The most common form of SGD was lupus nephritis (LN) (6.58% of all cases). FSGS (28.27%) and MCD (21.96%) were the most common lesions in males and females, respectively. In the age groups of 16-29 years, 30-59 years, and ≥60 years, MCD (28.96%), MN (24%), and MN (40.74%) were the most common lesions, respectively, followed by FSGS in all groups (25.68%, 24.5%, and 18.52%, respectively). Among the patients, 27.07% had serum creatinine ≥1.5 mg/dL and 28.54% had either macroscopic or microscopic hematuria. CONCLUSIONS: FSGS is increasingly becoming the most common cause of adult NS. This trend in Asia is seen predominantly in countries of the Indian subcontinent.

The outcome of treating ESBL infections with carbapenems vs. non carbapenem antimicrobials.

BACKGROUND: In India where the prevalence of extended spectrum beta lactamase (ESBL) producing organisms among gram negative organisms is 60-70% and Ertapenem was unavailable at the beginning of this study, exclusive use of Group 2 Carbapenems (Imipenem and Meropenem) for treatment raises issues of cost and development of resistance. Therefore the role of non-Carbapenem alternatives, chiefly Betalactam + Betalactamase inhibitors (BL-BLI) was explored in this prospective observational study at a private tertiary care teaching hospital. PATIENTS AND METHODS: 522 consecutive in door patients from the period between June 2006 to March 2007and June 2008 to December 2008, who had true infections with ESBL producing organisms were enrolled in the study. Antimicrobials were prescribed or changed by the treating physicians on the basis of the nature and severity of infection, the susceptibility of the organism and the affordability of the patient. Patients who received a Carbapenem at any time during treatment were considered in the Carbapenem group. Those who never received a Carbapenem at any time during treatment were considered in the non-Carbapenem group. RESULTS: Of the 522 infections, 287 were urinary tract infections, 60 were skin structure infections, 60 were bacteremias, 55 were hospital acquired pneumonias, 31 were intra-abdominal infections and 29 were other infections. There were 351 E. coli, 119 K. pneumoniae, 23 K. oxytoca, 16 Enterobacter aerogenes, 5 Kozoanae, 4 Enterobacter agglomerans, 3 Citrobacter freundi, 1 E. cloacae, 1 Enterobacterspp. and 1 Morgenella morganii isolates. Clinical outcomes were available for 486 patients. 339 patients who were in the non-Carbapenem group and who might have had less serious infections had a clinical success rate of 79.6%. 147 patients who were in the Carbapenem group and who might have had more serious infections had a clinical success rate of 85.71%. CONCLUSIONS: It is possible to successfully treat at least the less serious infections due to ESBL producing gram negative organisms with non-Carbapenem antimicrobials. This will not compromise outcomes but will likely result in restricting the use of Carbapenems which may help preserve their efficacy against increasingly resistant organisms.

Paraneoplastic Glomerular Diseases.

Paraneoplastic glomerular diseases (GNs) are rare manifestations in patients with underlying hematologic and solid organ malignancies and can occur before or after the detection of cancer. In the absence of established algorithms for investigation and reliable tests, they remain difficult to diagnose. Given the heterogeneity and infrequency of cases, the pathogenesis of most paraneoplastic GNs is poorly understood. Most of our recent understanding of paraneoplastic GNs has emerged from the discovery of target antigens in membranous nephropathy such as thrombospondin type-1 domain-containing protein 7A and neural epidermal growth factor-like 1 protein that appear to be promising in differentiating a primary vs paraneoplastic cause of membranous nephropathy. Treatment of paraneoplastic GNs is usually directed at the underlying malignancy. This review will focus on the epidemiology, pathogenesis, and diagnosis of paraneoplastic glomerular processes.

The Effect of Higher and Lower Protein Intakes on Nitrogen Balance in Renal Transplant Recipients with Underlying Graft Dysfunction.

It is essential to determine the optimum protein intake in renal transplant recipients on steroids with renal dysfunction to maintain a neutral nitrogen balance. Our aim was to study the effect of higher (1.2 g/kg/day) and lower (0.8 g/kg/day) protein intakes on nitrogen balance, body composition, glomerular filtration rate (GFR), and proteinuria in renal transplant recipients with low estimated GFR (eGFR) (15-44 mL/min/1.73 m2). This prospective, open-labeled, randomized, cross-over, interventional study enrolled patients who were ≥4 months posttransplant with eGFR between 15 and 44 mL/min/1.73 m2. Subjects were randomized to either Group 1 [Diet: proteins (1.2 g/kg/day), 35 kcal/kg/day] or Group 2 [Diet: proteins (0.8 g/kg/day) and 35 kcal/kg/day] for one month. Subjects crossed over to the other diet for 2nd month. Body composition analysis, serum creatinine, blood urea nitrogen, serum protein, serum albumin, 24-h proteinuria, GFR measurement (24 h creatinine clearance), three-day diet recall and nitrogen balance estimation were performed at baseline and at the end of the first and 2nd month. Statistical analysis was performed using IBM SPSS Statistics version 21. Thirty-two of 35 patients completed the study. Three-day diet recall showed that daily protein and energy consumption was 1.2 g/kg and 36.47 kcal/kg with higher and 0.94 g/kg and 31.94 kcal/kg with lower protein diets, respectively. Nitrogen balance was +3.61 g/day (P = 0.0002) with higher and +1.66 g/day with lower protein diets. A significant increase was noted in muscle mass (P = 0.0317), blood urea nitrogen (P = 0.0118), GFR (P = 0.0114), and proteinuria (P = 0.010) with a higher protein diet. Renal transplant recipients remained in positive nitrogen balance with both diets. Muscle mass and proteinuria increased significantly with a higher protein diet.

Kidney complications of parasitic diseases.

Parasitic agents have been known to cause human disease since ancient times and are endemic in tropical and subtropical regions. Complications of parasitic diseases, including kidney involvement, are associated with worse outcomes. Chagas disease, filariasis, leishmaniasis, malaria and schistosomiasis are important parasitic diseases that can damage the kidney. These diseases affect millions of people worldwide, primarily in Africa, Asia and Latin America, and kidney involvement is associated with increased mortality. The most common kidney complications of parasitic diseases are acute kidney injury, glomerulonephritis and tubular dysfunction. The mechanisms that underlie parasitic disease-associated kidney injury include direct parasite damage; immunological phenomena, including immune complex deposition and inflammation; and systemic manifestations such as haemolysis, haemorrhage and rhabdomyolysis. In addition, use of nephrotoxic drugs to treat parasitic infections is associated with acute kidney injury. Early diagnosis of kidney involvement and adequate management is crucial to prevent progression of kidney disease and optimize patient recovery.

A Unified Citywide Dashboard for Allocation and Scheduling Dialysis for COVID-19 Patients on Maintenance Hemodialysis.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused significant global disruption, especially for chronic care like hemodialysis treatments. Approximately 10,000 end-stage kidney disease (ESKD) patients are receiving maintenance hemodialysis (MHD) at 174 dialysis centers in Greater Mumbai. Because of the fear of transmission of infection and inability to isolate patients in dialysis centers, chronic hemodialysis care was disrupted for COVID-19-infected patients. Hence, we embarked on a citywide initiative to ensure uninterrupted dialysis for these patients. Materials and Methods: The Municipal Corporation of Greater Mumbai (MCGM) designated 23 hemodialysis facilities as COVID-positive centers, two as COVID-suspect centers, and the rest continued as COVID-negative centers to avoid transmission of infection and continuation of chronic hemodialysis treatment. Nephrologists and engineers of the city developed a web-based-portal so that information about the availability of dialysis slots for COVID-infected patients was easily available in real time to all those providing care to chronic hemodialysis patients. Results: The portal became operational on May 20, 2020, and as of December 31, 2020, has enrolled 1,418 COVID-positive ESKD patients. This initiative has helped 97% of enrolled COVID-infected ESKD patients to secure a dialysis slot within 48 hours. The portal also tracked outcomes and as of December 31, 2020, 370 (27%) patients died, 960 patients recovered, and 88 patients still had an active infection. Conclusions: The portal aided the timely and smooth transfer of COVID-19-positive ESKD patients to designated facilities, thus averting mortality arising from delayed or denied dialysis. Additionally, the portal also documented the natural history of the COVID-19 pandemic in the city and provided information on the overall incidence and outcomes. This aided the city administration in the projected resource needs to handle the pandemic.

Moral Distress and Moral Injury in Nephrology During the COVID-19 Pandemic.

Across the world, challenges for clinicians providing health care during the coronavirus disease 2019 (COVID-19) pandemic are highly prevalent and have been widely reported. Perspectives of provider groups have conveyed wide-ranging experiences of adversity, distress, and resilience. In understanding and responding to the emotional and psychological implications of the pandemic for renal clinicians, it is vital to recognize that many experiences also have been ethically challenging. The COVID-19 pandemic has prompted rapid and extensive transformation of health care systems and widely impacted care provision, heightening the risk of barriers to fulfillment of ethical duties. Given this, it is likely that some clinicians also have experienced moral distress, which can occur if an individual is unable to act in accordance with their moral judgment owing to external barriers. This review presents a global perspective of potential experiences of moral distress in kidney care during the COVID-19 pandemic. Using nephrology cases, we discuss why moral distress may be experienced by health professionals when withholding or withdrawing potentially beneficial treatments owing to resource constraints, when providing care that is inconsistent with local prepandemic best practice standards, and when managing dual professional and personal roles with conflicting responsibilities. We argue that in addition to responsive and appropriate health system supports, resources, and education, it is imperative for health care providers to recognize and prevent moral distress to foster the psychological well-being and moral resilience of clinicians during extended periods of crisis within health systems.

Transfemoral thrombolysis with thrombosuction: an aid to renal biopsy in a case of acute Budd Chiari syndrome complicating nephrotic syndrome.

Renal biopsy is usually a prerequisite in the diagnosis of adult patients with nephrotic syndrome. Acute Budd Chiari syndrome is a known complication of certain aetiologies of nephrotic syndrome like membranous glomerulopathy and minimal change disease. This complication requires emergent anticoagulation, which would preclude the performance of a renal biopsy. We report the case of a 47-year-old woman who presented with acute Budd Chiari syndrome as the initial presentation of nephrotic syndrome. The difficult situation in which we had to give anticoagulation and also perform a renal biopsy led us to devise a novel way to treat the patient, namely, the initial use of transfemoral thrombolysis and thrombosuction followed by a renal biopsy, which confirmed the diagnosis of primary membranous nephropathy. Anticoagulation was safely instituted 48 hours later with documented clinical and radiological improvement.

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.