Idiopathic hypereosinophilic syndrome presenting with stroke.

Hypereosinophilic syndrome (HES) is characterized by eosinophilia associated with organ damage. The disorder has substantial clinical heterogeneity and a highly variable prognosis. This report describes an interesting autopsy case of a 62-year-old lady presenting with itching and stroke-like symptoms. She was diagnosed with an "idiopathic" variant of HES after a thorough exclusion of all known causes. Despite adequate measures, she deteriorated rapidly. At autopsy, acute cerebral infarcts were identified in multiple vascular territories including infarcts in watershed areas. Additionally, her heart showed classic pathological features of eosinophilic myocarditis spanning all three stages.

Long-term complications in patients with childhood-onset nephrotic syndrome.

BACKGROUND: Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. METHODS: This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last [Formula: see text] 3 consecutive years without immunosuppressive medication to maintain remission. RESULTS: Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. CONCLUSIONS: In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at [Formula: see text] 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. A higher resolution version of the Graphical abstract is available as Supplementary information.

ANCA-associated vasculitis following ChAdOx1 nCoV19 vaccination: case-based review.

For the foreseeable future, vaccines are the cornerstone in the global campaign against the Coronavirus Disease-19 (COVID-19) pandemic. As the number and fatalities due to COVID-19 decline and the lockdown anywise rescinded, we recognize an increase in the incidence of autoimmune disease post-COVID-19 vaccination. However, the causality of the most vaccine-induced side effects is debatable and, at best, limited to a temporal correlation. We herein report a case of a 51-year-old gentleman who developed Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) 2 week post-COVID-19 vaccination. The patient responded favorably to oral steroids and rituximab. Additionally, we conducted a case-based review of vaccine-associated AAV describing their clinical manifestations and treatment response of this emerging entity.

Primary membranous nephropathy in children and adolescents: a single-centre report from South Asia.

BACKGROUND: Unlike adults, primary membranous nephropathy (PMN) comprises only 1-2% of childhood nephrotic syndrome. The clinical behaviour of PMN in children is not explicit and we report upon clinical presentation and outcome. METHODS: This prospective study includes children and adolescents (< 20 years) with biopsy-proven PMN without secondary causes. Anti-PLA2R assessment: before and after completing therapy. OUTCOME: percentage of patients achieving remission. RESULTS: Study cohort included 48 (M:F ratio 1.1:1) patients and median age 17 (IQR 15-18) years, with 35 (72.9%) PLA2R related. Median interval from symptom onset to presentation was 5 months, where median proteinuria, serum albumin and creatinine were 4.9 g/day, 2.1 g/dL and 0.63 mg/dL, respectively. Forty-seven patients received immunosuppressive therapy, with various agents used as first-line therapy: cyclical CYC/GC (53.1%), CNI/GC (21.3%), rituximab (14.9%), prednisolone alone (4.3%), azathioprine (4.3%) and mycophenolate mofetil (2.1%). Median follow-up was 29 (14, 59) months. At 6 months, 11 (24.4%) and 17 (37.7%) had complete remission (CR) or partial remission (PR), while at last follow-up (median 29 months), 20 (45.4%) and 14 (31.8%) had CR and PR respectively. No significant differences in outcome were observed with different agents. A total of 60% patients treated with rituximab as first line/for relapsing disease, and all cases with resistant disease receiving rituximab had CR or PR at last follow-up. PLA2R antibody presence was associated with clinical outcome. CONCLUSIONS: Three-quarters of PMN in children and adolescents is PLA2R related and two-thirds respond to immunosuppressive therapy. Rituximab is a promising agent to manage PMN in children. Anti-PLA2R is associated with clinical outcomes.

Rituximab in treatment of collapsing FSGS-A case series.

BACKGROUND: Collapsing focal segmental glomerulosclerosis (cFSGS) is an aggressive glomerular disease presenting as a nephrotic syndrome that has lower rates of remission with conventional immunosuppressive therapy and rapidly progresses to end-stage-renal-disease (ESRD). We report eight cases of HIV-negative cFSGS treated with rituximab. METHODS: The current report is a retrospective case series of cFSGS treated with rituximab from January 2011 to March 2020, at varying phases of the disease. RESULTS: Eight out of the 70 cFSGS patients received rituximab. The median age of patients was 30 years (IQR 24.25-37.5); five patients were males. The median serum creatinine, mean serum albumin and median 24 hours urinary protein at presentation was 0.9 (IQR 0.66-1.27) mg/dL, 2.95 ± 1.15 g/dL, 4.87 (IQR 1.64-5.75) g/day, respectively. Two patients were steroid-resistant, one steroid and tacrolimus dependent, one steroid and cyclosporine dependent, two steroids and tacrolimus resistant, one steroid, tacrolimus, cyclophosphamide, mycophenolate mofetil resistant and one steroid-resistant and tacrolimus dependent before rituximab therapy. Rituximab was given either as targeted therapy (after an initial dose of 375 mg/m2 ; patients having CD-19 levels >5/µL or >1% at 1 month received additional low-dose [100 mg] of rituximab), or weekly regimen. Five patients received CD-19 targeted rituximab; three received weekly doses of 375 mg/m2 , cumulative doses being 820 ± 228.03 mg, and 1800 ± 721.11 mg, respectively. At the end of median follow-up of 15 months, five (62.5%) patients were in remission (three partial, two complete remissions), two (25%) were resistant to therapy; one (12.5%) progressed to ESRD. CONCLUSION: Rituximab is reasonably safe and achieves/maintains remission in 60% of cFSGS cases.

Low-Dose Sofosbuvir Is Safe and Effective in Treating Chronic Hepatitis C in Patients with Severe Renal Impairment or End-Stage Renal Disease.

BACKGROUND AND AIMS: There is sparse data on the use of Sofosbuvir based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2. We evaluated the safety and efficacy of low-dose Sofosbuvir plus full-dose Daclatasvir in CHC patients with CKD. METHODS: Sixty-five CHC patients with CKD with eGFR less than 30 mL/min/1.73 m2 [54 (83%) patients with ESRD on hemodialysis] were included. All patients irrespective of genotype were treated with half-dose Sofosbuvir [200 mg (half tablet of 400 mg)] plus full-dose Daclatasvir (60 mg) given daily for either 12 or 24 weeks given in patients with genotype 3 cirrhosis. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12 weeks after the end of treatment (ETR). RESULTS: The median HCV RNA level in 65 patients (Males 40, mean age 42.9 ± 13 years) was 1.65 × 106 (1.2 × 103-1.73 × 108) IU/mL with 42 (64.6%) patients having HCV genotype 1, followed by genotype 3 and 2 in 22 (34%) and 1 (1.4%) patients, respectively. Twenty-one (32%) patients had evidence of cirrhosis, and ten (15.4%) patients were treatment experienced. Sixty-four (98.5%) patients achieved ETR, and 65 (100%) patients attained SVR12. All patients tolerated the DAAs well with none of the patients reporting any serious adverse events. Minor side effects noted were nausea seen in five (7.7%) patients, insomnia and headache in four (6.2%) patients each, and pruritus in one (1.5%) patient. CONCLUSION: Low-dose Sofosbuvir and full-dose Daclatasvir are safe and effective in treating CHC in patients with CKD with eGFR less than 30 mL/min/1.73 m2.

Membranous nephropathy with light chain restricted deposits.

The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M-type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow-up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow-up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non-malignant associated MN with monoclonal deposits on IF.

Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

BACKGROUND: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. METHODS: GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. RESULTS: A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to -0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m2. CONCLUSION: Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians.

BACKGROUND: Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. METHODS: A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by TaqMan assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. RESULTS: Of 114 patients, 66.7% showed elevated serum anti-PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti-PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. CONCLUSION: To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy.

Tacrolimus combined with corticosteroids versus Modified Ponticelli regimen in treatment of idiopathic membranous nephropathy: Randomized control trial.

AIM: There have been very few studies comparing cyclophosphamide (CTX) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy (NIST) resistant idiopathic membranous nephropathy (IMN). The present study was aimed at comparing the efficacy and safety of tacrolimus (TAC)/steroids with cyclical CTX/steroids (Modified Ponticelli regimen (MPR)) in patients with IMN. METHODS: Idiopathic membranous nephropathy patients (n = 70) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally randomized to receive TAC with oral prednisolone (TAC*) or MPR. Antibodies against m-type phospholipase A2 receptor (PLA2R Ab) were tested for at baseline and, at 6 and 12 months after the start of therapy. The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups. RESULTS: Intention-to-treat analysis showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; P = 0.30) and 12 months (71% with TAC* vs. 77% with MPR; P = 0.78) were comparable. PLA2R Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum albumin (r -0.49/-0.53) at the end of therapy. Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity. CONCLUSION: In NIST refractory IMN, both TAC* and MPR are comparable, but with different adverse effect profile. PLA2 R Ab has a very good association with proteinuria, and should be regularly monitored on clinical follow-up.

Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m-type phospholipase A2 receptor (PLA2R) are seen in two-thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti-PLA2R in paediatric IMN. We evaluated anti-PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti-PLA2R titer. The present report suggests that PLA2R has a contributory role in the pathogenesis of paediatric IMN.

Histopathological indicators of disease outcome in class IV lupus nephritis: a revisit of various indices.

Current management guidelines for lupus nephritis (LN) do not attach importance to histological indices of disease activity or chronicity. The present study was performed to evaluate the clinical relevance of these indices in determining outcomes in patients with class IV LN. We analyzed the data of all patients with biopsy-proven class IV LN seen over a 6-year period. The histopathological findings were reviewed; the activity and chronicity indices proposed by Austin [AI (Austin) & CI (Austin)] and the renal biopsy index proposed by Hill were calculated. As immunofluorescence was not done in all patients, this was excluded from calculation of the renal biopsy index, which was referred to as the modified Hill's index (MHI), which was a composite of glomerular activity index (GAI), chronicity index (CI) and tubulo-interstitial activity index (TIAI). Pearson's correlation coefficient, multilinear regression analysis and logistic analysis were performed, and p value of <.05 was considered significant. During the study period, 114 cases of LN were evaluated, of which 64 % (73/114) had class IV LN. The mean age was 26.5 years, and 92 % were females. The mean scores of AI (Austin), CI (Austin), GAI, CI, TIAI and MHI were 8.46, 2.50, 7.54, 3.06, 4.74 and 2.23, respectively. Serum creatinine correlated significantly with TIAI, CI, CI (Austin) as well as MHI, but not with AI (Austin) or GAI. The serum creatinine level was the strongest clinical parameter determining outcome, while none of the histological indices correlated with either treatment outcome or mortality. None of the histological indices performed better than serum creatinine level in determining the treatment outcomes and mortality.