Effectiveness of Lactoferrin in the Treatment of Anemia in Chronic Kidney Disease: A Single-Center Pilot Study.

Background: Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD). Materials and Methods: In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks. Results: A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level. Conclusion: Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.

Role of Desmopressin Acetate before Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with Kidney Dysfunction.

Background: The most common complication of percutaneous kidney biopsy is bleeding, which can be seen in up to one-third of cases. The aim of this study was to evaluate the effect of prebiopsy administration of intranasal desmopressin acetate in reducing the incidence of biopsy-related bleeding complications. Materials and Methods: This was a prospective randomized double-blind pilot study conducted at our center from January 2021 to September 2022. Consecutive adult patients who underwent native percutaneous kidney biopsy with an estimated glomerular filtration rate (eGFR) ≤45 ml/min/1.73 m2 were randomized into a placebo (saline intranasal spray) group versus intranasal desmopressin group. The bleeding complications were compared between the two groups. Results: A total of 80 patients who underwent kidney biopsy at our center from January 2021 to September 2022 with eGFR ≤45 ml/min/1.73 m2 were included (40 patients in desmopressin group and 40 patients in non-desmopressin group) in the study. The mean age of the patients was 44 ± 12 years with a mean eGFR of 20.82 ± 12.64 ml/min/1.73 m2. Intranasal desmopressin administration before kidney biopsy was associated with a significantly higher number of minor bleeding complications (P = 0.02) and no significant reduction in major complications (P = 0.15) when compared with a group that did not receive desmopressin. Other complications like hypotension, flushing, and vasovagal syncope were not statistically significantly associated with the use of desmopressin. Conclusion: Our study did not find any utility of prophylactic desmopressin use before kidney biopsy in patients with kidney dysfunction.

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.

IL-23/IL-17 in a Paradoxical Association with Primary Membranous Nephropathy.

Primary membranous nephropathy (PMN), an autoimmune disease, is the most common cause of nephrotic syndrome in middle-aged non-diabetic adults. PMN pathophysiology includes Th1/Th2 paradigm. The IL-23/IL-17 pathway is implicated in autoimmune kidney disorders, but no study has examined its relationship with PMN. In several unrelated studies, PMN patients reported to have paradoxical IL-17 levels. This manuscript describes the best possible association of IL-23/IL-17 axis with PMN. Biopsy-proven PMN patients and age, gender-matched healthy controls were enrolled. Serum-PLA2R (Euroimmune, Germany), IL-23 and IL-17 (R&D; USA), was measured using ELISA along with biochemical parameters. Appropriate statistical tools were used for analysis. One hundred eighty-nine PMN patients (mean age 41.70 ± 12.53 years) and 100 controls (mean age 43.92 ± 10.93 years) were identified. One hundred forty were PLA2R-related. PMN patients had median proteinuria, serum albumin, and creatinine of 6.12 (3.875, 9.23) g/day, 2.32 (1.96, 2.9) g/dl, and 0.89 (0.7, 1.1) mg/dl, respectively. IL-17, but not IL-23, was significantly increased in PMN patients compared to controls (IL-17, median: 12.07 pg/ml (9.75, 24.56) vs median: 9.75 pg/ml (8.23, 17.03) p = 0.0002); (IL23, median: 6.04 pg/ml (4.22, 10.82) vs median: 5.46 pg/ml (3.34, 9.96) p = 0.142). IL-17 and IL-23 correlated significantly (p 0.05) in PMN patients, and similar trend was seen when grouped into PLA2R-related and -unrelated groups. The levels of IL-23 (p = 0.057) and IL-17 (p = 0.004) were high in MN patients that did not respond to the treatment. The current finding may indicate or suggest the involvement of IL-23/IL-17 PMN pathogenesis. A comprehensive investigation is needed to evaluate IL-23/IL-17 axis with renal infiltrating immune cells, and external stimuli.

Circulating "Neutrophils extra-cellular traps" during the early post-renal transplant period and correlation with graft dysfunction and rejection.

BACKGROUND: Neutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI. METHODS: Prospectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome. RESULTS: Circulating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01-0.19) to 0.51 (0.22-0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12-0.27) to 0.38 (0.19-0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18-0.72) and 0.35 (0.26-0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13-0.31) to 0.38 (0.28-1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74-12.56) µM to 17.37 (9.11-22.25) µM; p = 0.03 in group-A, and 8.7 (6.04-10.30) µM to 14.66 (13.39-21.63) µM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64-13.90) µM and 11.11 (9.15-17.54) µM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both. CONCLUSION: Circulating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.

Novel Flow Cytometry-Based Method for Detection of Anti-HLA Complement Activating Donor-Specific Antibodies in Renal Transplant Recipients and Its Comparison With Other Conventional Detection Methods.

BACKGROUND: Presence of preformed donor specific antibodies (DSAs) detected by complement-dependent cytotoxicity (CDC-XM) is a strong contraindication for transplant. However, it has limitations including its sensitivity and its inability to distinguish between HLA-specific and other non-HLA-specific antibodies. In this study, we standardized CDC-XM by flow cytometry and determined its relevance by comparing its results with other methods of DSA detection, such as routine CDC-XM, antibody binding assay by flow cytometry (FC-XM), and Luminex-based crossmatch assays, such as Luminex crossmatch (LXM) and virtual crossmatch (VXM). MATERIALS AND METHODS: A total of 79 serum samples were tested for DSAs by the flow cytometric complement-dependent cytotoxicity crossmatch assay (FC-CDC-XM) and then the results of FC-CDC-XM were compared with other detection methods such as CDC-XM, FC-XM, LXM, and VXM. RESULTS: We found that the FC-CDC-XM assay is more sensitive than routine CDC-XM. Out of total 79 sera, 24 sera were detected positive (T cells positive: 1 case and B cells positive: 23) by FC-CDC-XM as compared with 3 sera using CDC-XM; these 3 sera also showed positivity by FC-CDC-XM. After FC-XM assay, 23 samples were positive by FC-XM and out of these 23 samples, 13 were also positive by FC-CDC-XM. On comparing the FC-CDC-XM results with VXM and LXM, 10 sera of 24 FC-CDC-XM positive had HLA class II antibodies detected on a Luminex platform. CONCLUSIONS: The FC-CDC-XM is a more sensitive and specific method for detection of HLA-specific complement-fixing antibodies than CDC-XM and FC-XM. FC-CDC-XM should be used in tissue-typing laboratories after intra- and inter- laboratory validation.

A randomized trial of once daily versus twice daily dosing of oral iron in CKD.

We investigated the effect of two dosing regimens of oral iron on iron status and hematological parameters in patients with CKD. In this single center, open label, randomized, active controlled clinical trial, stable adult patients with CKD stage G3-4 with percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml were eligible. Participants were randomized to receive either 100 mg of ferrous ascorbate once daily (OD group) or 100 mg of ferrous ascorbate twice daily (BD group, total daily dose 200 mg). The primary outcome was change in %TSAT between groups over 12 weeks. The secondary outcomes were changes in other iron status and hematological parameters, serum interleukin-6 (IL-6) and hepcidin. 80 participants were enrolled out of which 76 completed the study. Change in %TSAT was not significantly different between groups (ß = - 1.43, 95% CI - 3.99 to 1.12, BD group as reference). The rise in serum ferritin was less in the OD group as compared to BD group (ß = - 0.36, 95% CI - 0.61 to - 0.10) whereas MCHC increased in the OD group as compared to decrease in the BD group (ß = 0.37, 95% CI 0.067-0.67). These observations need exploration to ascertain the impact of different oral iron dosing strategies in CKD.

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.

Serum myo-inositol oxygenase levels at hospital discharge predict progression to chronic kidney disease in community-acquired acute kidney injury.

Acute kidney injury (AKI) increases the risk of morbidity, mortality, and progression to chronic kidney disease (CKD). There are few data on the risk of CKD following community-acquired AKI (CA-AKI) and its predictors from developing countries. We evaluated the association of a panel of serum and urine biomarkers at the time of hospital discharge with 4-month renal outcome in CA-AKI. Patients of either sex, aged between 18 and 70 years, with no underlying CKD, and with CA-AKI were recruited at the time of discharge from hospital in this prospective observational study. Levels of serum and urine biomarkers were analyzed and association between these markers and development of CKD, defined as eGFR < 60 ml/min/1.73 m2 or dialysis dependence at 4 month after discharge, were analyzed using multivariate logistic regression analysis and penalized least absolute shrinkage and selection operator logistic regression. Out of a total 126 patients followed up for 4 months, 25 developed CKD. Those who developed CKD were older (p = 0.008), had higher serum creatinine (p < 0.001) and lower serum albumin (p = 0.001) at discharge. Adjusted logistic regression showed that each 10% increase in standardized serum myo-inositol oxygenase (MIOX) level increased the odds of progression to CKD by 13.5%. With 10% increase in standardized urine Neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine and urine protein creatinine ratio (uPCR), increase in the odds of progression to CKD was 10.5%, 9.6% and 8%, respectively. Multivariable logistic model including serum MIOX, discharge serum creatinine and discharge uPCR, was able to predict the progression of CKD [AUC ROC 0.88; (95% CI 0.81, 0.95)]. High level serum MIOX levels at the time of discharge from hospital are associated with progression to CKD in patients with CA-AKI.

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.