Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Clinical Characteristics of Patients with Ckd Crash Landing and Initiating Dialysis Is it Time for Mandatory Screening Programme for Detection of CKD?

The present study was undertaken to study clinical, biochemical and echocardiographic characteristics of patients with Chronic Kidney Disease crash- landing and initiating hemodialysis at first presentation in our centre. MATERIAL: Ours was a cross-sectional study of one hundred and seventy patients with chronic kidney disease starting hemodialysis. Detailed history and examination were done. Apart from routine biochemical tests and CKD-MBD profile, all patient underwent ultrasonography, urine examination and echocardiography. Efforts were made to delineate etiology in each patient. OBSERVATION: Out of 170 patients 64% were males, 36% were females. Mean age at presentation in our study was 41.27 (±16.47) yrs. Chronic glomerulonephritis was the most common etiology accounting for 54% of cases followed by Diabetes (20%). Mean eGFR at presentation was <5 ml/min/1.73 m². Hypocalcemia was present in 87.1%, hyperphosphatemia in 84.2% and elevated PTH levels in 98% with mean PTH levels being 588.07±309.58 ng/ml. LVH on echocardiogram was present in 58.4 % of patient with diastolic dysfunction being reported in 31 % of patients. DCM was present in 28% of patients and 21% of patients had frank left ventricular failure at presentation. CONCLUSION: Chronic Kidney Disease patients referred late have clinical and lab characteristics which are worse as compared to routine CKD patients .This calls for a mandatory CKD screening programme for increasing awareness and early identification of CKD patients.

Role of Rituximab in Patients with Resistant Nephrotic Syndrome.

Resistant nephrotic syndrome is a group of disorders with diverse histological findings, which are by definition resistant to corticosteroids given in adequate dose for adequate duration and many are resistant to other therapy as well. In many patients progression to end-stage renal disease is the ultimate outcome. The role of B cells has not been fully explained in man, agents that specifically interfere with B cells would ideally represent the first step toward selective therapy. We studied short term and long term effects of rituximab in patients with resistent primary nephrotic syndrome. MATERIAL: Study was conducted at SMS-medical college and Hospital Jaipur, four doses of rituximab were given weakly, in fixed dose of 500 mg per dose and proteinuria was evaluated before start of therapy and at 3 months, 6 months and 12 months of therapy. Patients with resistant primary nephrotic syndrome who failed to respond to other therapies, with stable eGFR >30, and controlled BP were included in study. Patients with Active infection, Uncontrolled hypertension, pregnancy were excluded from study. OBSERVATION: 10 patients were enrolled in study out of which 7 FSGS (focal segmental glomeruloscllerosis) and 3 were IMN (idiopathic membranous nephropathy), 5 were female and 5 were male, age 17-61years (average 34.6), weight were 48-70 kg (avg 57.9), BMI 19.4-23 (AVG 21.18), all patients have normal renal function (average creatinine value of 0.8, range= 0.5 to 1.1). At 3 months 1 patient had partial response and 9 had no response. At 6 months of treatment 2 patients had partial response, 3 had complete response and 5 no response. At 12 months of treatment 4 had partial response, 5 had complete response and 1 no response. Out of 10 patients no one had relapse of Nephrotic syndrome at 12 month of therapy. Renal function remain normal in all patients over 12 months followup. CONCLUSION: This prospective, observational study evaluated 3 month, 6 month, and 12 month outcome of 3 IMN and 7 FSGS patients, with persistent nephrotic range proteinuria and showed that rituximab promoted sustained remission in proteinuria in resistent nephrotic syndrome with normal renal function.

Spectrum of Non diabetic kidney disease in patients with type 2 diabetes and its clinicopathological correlation.

Diabetes mellitus (DM) is the leading cause of chronic kidney disease worldwide chiefly attributable to diabetic nephropathy (DN). In these patients, non diabetic kidney disease (NDKD) can also occur either alone or superimposed on diabetic nephropathy. This study aimed to identify the prevalence and the etiology of NDKD in our center and also the clinical and laboratory parameters to help distinguish these two entities. MATERIAL: This was a cross sectional observational study. A total of 47 patients were enrolled in the study during the study period. In all the patients, kidney biopsy was done because of atypical presentations and was examined by light and immunofluorescence microscopy. The clinical & laboratory parameters and the biopsy findings were recorded in a standard proforma. OBSERVATION: A total of 47 patients (male/female: 34/13 and mean age 52.11±9.36) were included in the study. The chief co morbidity was hypertension which was present in 61.7% of patients. The most common indication of biopsy was nephrotic presentation (38.3%) followed by nephritic illness (25.5%). The prevalence of NDKD in our study cohort was 85.1% of which isolated NDKD was 57.4% and NDKD + DN was 27.7%. The most common histological lesion were membranous glomerulopathy and focal segmental glomerulosclerosis (FSGS) each with a frequency of 15% followed by chronic tubulointerstitial nephritis (CTIN), IgA nephropathy and others. There was significant difference in the median duration of diabetes in these groups and it was around 5 years less in the NDKD group. There was no difference among three groups in term of eGFR, HbA1C and proteinuria. CONCLUSION: Our study demonstrated a high prevalence of NDKD in the patients with type 2 diabetes. The duration of diabetes was the strongest predictor of NDKD. Kidney biopsy should be undertaken liberally whenever there is strong clinical suspicion especially in the presence of atypical features. The exact histological diagnosis can clarify the further treatment planning as well as the prognosis.

Gerontolizing Nephrology: Spectrum of Histopathological Findings of Kidney Biopsy in the Elderly.

INTRODUCTION: The spectrum of renal disorder in the elderly differs from the younger population. There is a paucity of literature regarding kidney biopsy in elderly. This study aims to highlight the clinical profile and histopathological spectrum of the elderly patient undergoing a renal biopsy. MATERIALS AND METHODS: This retrospective study included all patients (age ≥60 years) undergoing native renal biopsies from January 2012 to December 2017. The clinical profile, laboratory parameters, and renal biopsy findings of these patients were recorded from the case files. RESULTS: Out of 1656 renal biopsies performed during the study period, 230 (13.9%%) performed on the elderly were included. Mean age was 64.02 ± 7.87 years (Range: 60-87 years), and males were predominant (70.4%). The commonest indication for biopsy was nephrotic syndrome (NS) (49.6%) followed by Rapidly progressive renal failure (RPRF) (20.9%) and Acute Kidney Injury (AKI) (15.7%). The most frequent histological diagnosis was membranous nephropathy (15.2%) followed by amyloidosis (13.9%) and Focal Segmental Glomerulosclerosis (FSGS) (13.0%). The commonest cause of NS was MGN (29.8%) followed by FSGS (24.6%) and amyloidosis (22.8%). The commonest cause of nephritic syndrome was Diffuse Proliferative Glomerulonephritis (29.4%) and Membranoproliferative Glomerulonephritis (29.4%). Hypertensive nephrosclerosis (40.0%) and diabetic nephropathy (26.7%)) were the commonest histological diagnosis in the patients who underwent renal biopsy for clinical Chronic kidney disease. Crescentic GN (35.4%) and Myeloma cast nephropathy 14.6%) were the commonest cause of RPRF while Acute Tubular Necrosis (41.7%) was the commonest cause of AKI. None of the patients had major complications. CONCLUSION: Renal biopsy is safe in the elderly and provides a wealth of information with regards to the diagnosis and prognosis of renal disorder.

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.

Lower Limb Nodulo-ulcerative Lesion in Kidney Transplant Recipient - An Unusual Diagnosis.

A 56-year-old kidney transplant recipient presented with a progressive cauliflower-like growth on the plantar surface of the right foot and on workup found to have chromoblastomycosis, which was successfully treated by antifungal agent and surgical excision with no recurrence. Chromoblastomycosis belongs to the heterogeneous group of subcutaneous mycoses. It is caused by various pigmented (dematiaceous) fungi, which gain entry into the skin via traumatic implantation. The case is of interest because it has so far not been reported from the northwest arid zone of India in kidney transplant recipients.

Characteristics and outcome of postpartum acute kidney injury requiring dialysis: A single-center experience from North India.

Postpartum acute kidney injury (AKI) is one of the serious complications of pregnancy and is associated with high mortality and morbidity. We conducted this study to determine the characteristics and outcome of the most severe form of postpartum AKI requiring dialysis. This prospective, observational study was conducted in Sawai Man Singh Medical College, Jaipur. All postpartum female suffering from AKI requiring dialysis between July 2014 and December 2016 were included in the study. Demographic, clinical and laboratory data of the patients were recorded. Outcome variables included survival at hospital discharge and estimated glomerular filtration rate (eGFR) at three months of follow-up. Sixty (88.2%) out of 68 women admitted with postpartum AKI required dialysis. The mean age was 26.5 ± 4.3 years and the majority (80%) had institutional delivery. The mean sequential organ failure assessment (SOFA) score was 8.0 ± 2.9. Puerperal sepsis (n = 37, 61.6%), preeclampsia (n = 21, 35%), and antepartum hemorrhage (n = 14, 23.3%) were the most common obstetric complication associated with postpartum AKI. Maternal mortality was 28.3%. Higher SOFA score (P = 0.015, odds ratio [OR]: 1.99, confidence interval [CI]: 1.14-3.45) and diagnosis of sepsis (P = 0.048, OR: 26.3, CI: 1.03-678.3) were the independent predictors of mortality. Out of 37 patients who were followed up at three months, 51.3% had eGFR <60 mL/min/1.73 m2. Duration of anuria (in days) was the only independent predictor of (eGFR <60 mL/min/1.73 m2 at three months of follow-up (P = 0.029, OR: 1.2, CI: 1.02-1.46). Postpartum AKI requiring dialysis was associated with high mortality. More than half of the survivors had eGFR <60 mL/min/1.73 m2 on follow-up highlighting the need of appropriate follow-up.

Comparison of intradermal route and dose of Hepatitis B vaccine administration in chronic dialysis patients: A pilot study.

We aimed to study the seroconversion rate in two arms of intradermal (ID) route: low dose with high-frequency and high dose with low-frequency hepatitis B (HB) vaccination in dialysis patients. A total of 56 patients, on either hemodialysis or peritoneal dialysis, were included. Patients were enrolled and randomized into two groups. The first group was immunized through the ID route and received weekly 10 µg of vaccine at 0, 1, 2, 3, 4, 5, 6, and 7 weeks (low-dose with high frequency). The second group was immunized through the ID route and received two doses of 40 µg at one-month interval (high dose with low frequency). Anti-HBs antibody titers were measured at one month and one month after completion of the vaccination, i.e., at three months in each group. At one month, each group had received 40 µg of vaccine. The seroconversion rate was 28.57% in each group. At one month after completion of vaccination, seroconversion rate in low-dose ID and high-dose ID was 60% and 58.33%, respectively (P = 0.911) at 80 µgm of total vaccine dose. The overall "good" responders in low-dose versus high-dose ID route were 30% and 50%, respectively (P = 0.179). However, among responders, anti-HBs antibody titers ≥100 mIU/mL in low-dose and high-dose ID route were 50% and 85.7%, respectively (P = 0.049). The rate of seroconversion is comparable in both low dose with high-frequency and high dose with low-frequency ID route.

Leukocyte esterase reagent strip as a bedside tool to detect peritonitis in patients undergoing acute peritoneal dialysis.

Peritonitis is a common and life-threatening complication of acute peritoneal dialysis (PD). Diagnosis requires the presence of clinical signs of peritonitis which are nonspecific and laboratory investigations [total leukocyte count (TLC), Gram-stain, and culture of PD effluent fluid] which are time-consuming and not available at the bedside. In this study, we evaluated the use of leukocyte esterase reagent strip (LERS) as a bedside test to diagnose peritonitis in patients undergoing acute PD. Patients who underwent acute PD were monitored for signs and symptoms of peritonitis. PD effluent fluid analysis included TLC, absolute neutrophil count, Gram-stain, and culture for the diagnosis of peritonitis. LERS (Multistix 10SG) was simultaneously dipped in PD effluent fluid and read at two minutes. Reading of + was considered as indicative of peritonitis. Twenty-one out of 166 (12.6%) patients undergoing acute PD developed peritonitis. LERS detected peritonitis in 20 patients. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of LERS were 95.2%, 95.2%, 74.1%, and 99.3%, respectively. LERS has very high sensitivity and NPV and can be used as a rapid bedside tool to exclude peritonitis in patients undergoing acute PD.

Clinicoepidemiological profile of peritonitis complicating acute peritoneal dialysis: A single-center experience.

A prospective observational study examining the incidence and microbiological aspects of peritonitis complicating acute intermittent peritoneal dialysis (IPD) was performed. A total of 145 acute IPD treatments were included involving 112 patients. The majority of patients suffered from acute kidney injury (72.3%) secondary to sepsis. Peritonitis occurred in 31 treatment sessions, giving a frequency of 21.4% of procedures performed. The mean interval between starting dialysis and the first sign of peritonitis was 2.9 days, with 58% of cases occurring in the Intensive Care Unit. Frequent catheter manipulation/repositioning and leakages were identified as significant predisposing factors for peritonitis, and the risk of peritonitis was increased with longer duration of IPD. Gram-negative infections were more common than Grampositive infections. The use of systemic antibiotics did not prevent the development of peritonitis.

Profile of glomerular diseases associated with hepatitis B and C: A single-center experience from India.

Hepatitis B and C are known to affect kidneys in a number of ways. Glomerular diseases associated with hepatitis B and C include membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis, immunoglobulin A nephropathy, rarely amyloidosis, and fibrillary and immunotactoid glomerulopathy. In a retrospective analysis of kidney biopsy of 534 patients, we found 16 (2.9%) patients of hepatitis B and 11 (2.05%) patients of hepatitis C with glomerular disease. The most common form of glomerulonephritis in hepatitis B patient was MN and in hepatitis C patient was MPGN.

A clinicopathologic study of glomerular disease: A single-center, five-year retrospective study from Northwest India.

Studies published from centers across India have reported different and contradicting patterns of glomerular disease. In this retrospective study, we report our experience from a Tertiary Care Center in Northwest India. A total of 702 renal biopsies performed between 2008 and 2013 were reviewed of which 80 were excluded from the study because of having insufficient records or if the biopsies were taken from an allograft. The study included 411 males (66.1 %) and 211 females (33.9%) with an age range of 12-70 years (mean 30.34 ± 7.04 years). Majority of the biopsies (93.9%) showed some form of glomerulonephritis (GN), either primary (79.4%) or secondary glomerular disease (SGD) (14.5%). Minimal change disease (MCD) was the most common type of primary GN (26.5% of primary GN), followed by membranous nephropathy (MN; 18.8%) and focal and segmental glomerulosclerosis (FSGS; 13.2%). Lupus nephritis (LN) was the most frequent SGD (52.2% of secondary GN). Amyloidosis was found in 41.1% and diabetic glomerulosclerosis in 4.4%. LN was also the second most common diagnosis in females after MCD, seen in 19.4% of females. MCD followed by membranoproliferative GN and diffuse proliferative GN were the most common entities in individuals <20 years of age. In the 20-39 years age group, MN was the most common pathology seen. MN was again the most common pathology seen in patients aged above 40 years followed by amyloidosis and FSGS. In this study, MCD was the most common primary GN observed overall from this part of India. MN was the most common GN in individuals above 20 years of age presenting with the nephrotic syndrome. The geographical and regional differences in the pattern of GNs point to the necessity of having a central biopsy registry.

Gitelman's syndrome presenting with hypocalcemic tetany and hypokalemic periodic paralysis.

Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by hypomagnesemia, hypokalemia, hypocalciuria, and metabolic alkalosis. Hypocalcemic tetany as a presentation of Gitelman's syndrome has rarely been reported in literature. We report a rare case of Gitelman's syndrome presenting with hypocalcemic tetany along with hypokalemic periodic paralysis. A 17-year-old female was admitted to our hospital with a history of perioral numbness and carpal spasms of five days duration with progressive quadriparesis developing over a period of few hours. Past history was significant for three episodes of transient lower limb weakness. On examination, blood pressure was 110/70 mm Hg. Chvostek's sign and Trousseau's sign were positive. Neurologically, she was fully oriented. She had Grade 3 power in all the four limbs with intact sensation. Laboratory tests showed hypocalcemia (7.8 mg/dL), hypokalemia (2.2 mEq/L), hypomagnesemia (0.9 mEq/L), and hypocalciuria (104 mg/day). Arterial blood gas showed mild metabolic alkalosis with respiratory compensation. Thus, a clinical diagnosis of GS was made. The patient made a remarkable recovery after the correction of electrolyte imbalance. The aim of this case report is to re-emphasize the fact that hypocalcemia can rarely occur in Gitelman's syndrome.

Effect of vitamin D level on the immunogenicity to hepatitis B vaccination in dialysis patients.

We undertook this study to assess the response of hepatitis B vaccination in dialysis patients and the effect of vitamin D level on the immunogenicity to hepatitis B vaccination. It was an observational study, which included 60 patients of end-stage renal disease on maintenance dialysis. Patients with anti-HBs antibody positive at baseline were excluded. All received intramuscular recombinant hepatitis B vaccination at 0, 1, 2, and 6 months 20 µg on each deltoid muscle bilateral. Anti-HBs antibody titers were measured at 4 and 7 months of vaccination and the titer ≥10 mIU/mL was considered as "positive". Vitamin D levels were measured at baseline before starting the vaccination. The mean vitamin D level was 15.0 ± 7.8 ng/mL. The vitamin D level <10 and <20 were 23.3% and 83.3%, respectively. The patients on hemodialysis had relatively higher vitamin D level than on peritoneal dialysis patients, i.e. 16.3 ± 8.5 and 11.5 ± 3.1 ng/mL, respectively (p = 0.03). Overall, 38 patients responded to the immunization (63.3%) and 11 patients were non-responders (36.7%) at 4 months. Difference of vitamin D level in responder (16.6 ± 9.1 ng/mL) and non-responder (12.4 ± 4.1 ng/mL) was not significant (p = 0.16). At 7 months (1 month after completion of vaccination) 61.9% were responders and 38.1% were non-responders. The vitamin D level in responders and non-responders were statistically not significant (p = 0.11). In responder, titer ≥100 mIU/mL was seen in 30% at 4 months and in 42.9% at 7 months (p = 0.05). In the good and weak responders at 7 months, vitamin D levels were 21.5 ± 10.8 and 10.1 ± 3.7 ng/mL, respectively (p = 0.37). The association of vitamin D level and anti-HBs antibody titer were not significant (r = 0.03 and 95% CI was -0.43 to 0.48, p = 0.89) in those who responded. Most patients on dialysis were vitamin D deficient. Vitamin D levels did not differ between responding and non-responding dialysis patients.

Plasmodium vivax induced hemolytic uremic syndrome: An uncommon manifestation that leads to a grave complication and treated successfully with renal transplantation.

We are reporting a case of hemolytic uremic syndrome, a rare manifestation of Plasmodium vivax malaria. A young driver was admitted with acute febrile illness, decreased urine output, anemia, thrombocytopenia, jaundice, and increased serum lactate dehydrogenase. He showed a partial response to antimalarial drugs. However, he was readmitted with worsening renal parameters. His kidney biopsy revealed chronic thrombotic microangiopathy. He remained dialysis dependent and later underwent renal transplantation successfully, with excellent graft function at 1-year.

Outcomes of anatomical versus functional testing for coronary artery disease.

BACKGROUND: Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS: We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS: The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P=0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS: In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.).