Hepcidin and proinflammatory markers in children with chronic kidney disease: A case-control study
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BACKGROUND: Hepcidin is the main regulator of hepcidin-ferroportin axis and is elevated in children with chronic kidney disease (CKD). Anemia of CKD and its relation to hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in iron- and erythropoietin (EPO)-naïve, non-dialyzed children with CKD is under-studied. MATERIALS AND METHODS: This case-control study aimed to study the levels of hepcidin and other proinflammatory markers (IL-6, TNF-α, hs-CRP) and their relation with anemia in iron- and erythropoietin-naïve, non-dialysis CKD (stage 3 - 5) patients. 32 pediatric CKD stage 3 - 5 patients aged 2 - 18 years without previous iron or EPO therapy were compared with 32 gender- and age-matched healthy controls. The CKD cases were also divided into three categories based on their serum ferritin levels and transferrin saturation (%TSAT): true iron deficiency, impaired iron trafficking, and no iron deficiency. The baseline iron status was then correlated with the serum hepcidin levels. RESULTS: Serum hepcidin, IL-6, and TNF-α levels were significantly elevated compared to controls. As CKD stage progressed, hemoglobin levels decreased, while serum hepcidin, IL6, TNF-α and hs-CRP levels increased significantly. Serum hepcidin levels correlated positively with IL-6 (r = 0.57, p = 0.001), TNF-α (r = 0.34, p = 0.05), hs-CRP (r = 0.36, p = 0.03), and ferritin (r = 0.07, p = 0.001), while being inversely correlated with Total iron binding capacity (TIBC) (r = -0.50, p = 0.003), hemoglobin (r = -0.52, p = 0.001), and glomerular filtration rate (GFR) (r = -0.71, p = 0.000). Serum hepcidin levels were highest in those with impaired iron trafficking, followed by those with no iron deficiency, followed by those with absolute iron deficiency (55.16 vs. 49 vs. 11.8, p = 0.005). Amongst those with no iron deficiency, hepcidin correlated negatively with hemoglobin (r = -0.752, p-value = 0.007). CONCLUSION: A positive correlation between hepcidin and other inflammatory biomarkers in non-dialyzed, iron- and EPO-naïve pediatric CKD patients suggests a role of these markers in higher hepcidin production and its contribution to iron-restricted erythropoiesis across the spectrum of CKD. Median hepcidin levels were highest in those with impaired iron trafficking, followed by those with no iron deficiency, followed by those with absolute iron deficiency, suggesting that in an iron-replete state, high hepcidin levels inhibit iron absorption from the gut and release from iron storing cells, thus restricting erythropoiesis leading to anemia.
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BK polyomavirus infection after renal transplantation: Surveillance in a resource-challenged setting.

BACKGROUND: There is a paucity of data available about BK polyomavirus (BKPyV) infection after renal transplantation (RTX) in resource-limited countries with a predominantly living-donor, ABO-compatible RTX program. We aimed to assess BKPyV infection in such patients in a public hospital in India. METHODS: We prospectively evaluated plasma BKPyV replication in 62 patients at 1, 3, 6, 9, and 12 months after RTX. Sustained significant BK viremia (SSBKV) was defined as significant viremia (≥10 000 copies/mL) detected ≥2 times, and BKPyV-associated nephropathy (BKVAN) as histologic changes of BKVAN with BK viremia with/without graft dysfunction. RESULTS: All patients underwent RTX without requiring desensitization. Incidence of BK viremia was: 17.7%, 41.9%, 16.1%, 25.8%, and 17.7% at 1, 3, 6, 9, and 12 months, respectively. Of 62 patients, 64.5% had BKPyV viremia during the study, 32.2% had significant viremia, all except one detected in the first 6 months. Nine (14.5%) patients had SSBKV. There was no biopsy-proven BKVAN. At the end of 1 year, mean serum creatinine was higher and graft dysfunction was significantly more common in patients with SSBKV compared to those without SSBKV. CONCLUSION: Transient BK viremia is common in low/intermediate immunologic risk RTX recipients in India, with a peak occurring at 3-6 months. Most clear their viremia by 12 months. Graft dysfunction seems to be more frequent in patients with SSBKV, although BKVAN is uncommon on biopsy in these patients.

Subclinical non-autoimmune hypothyroidism in children with steroid resistant nephrotic syndrome.

BACKGROUND: Thyroid status has not been studied well in children with steroid resistant nephrotic syndrome (SRNS). METHODS: In this cross sectional study we recruited 20 children aged 1-16 years with SRNS and similar number of controls. Serum levels of FT3, FT4 and TSH were measured in all the subjects. Overt hypothyroidism was defined as low FT4 (normal values: 0.7-2.0 ng/mL) and elevated serum TSH above reference values (0.45-4.5 mIU/L). Subclinical hypothyroidism (SH) was defined as an elevation in serum TSH with a normal serum FT4 concentration. The primary outcome measure was serum levels of FT3, FT4 and TSH in children with SRNS. RESULTS: Thirty per cent of the children (n = 6) with SRNS had non-autoimmune subclinical hypothyroidism (2 children each with grade I, II and III). Children with SRNS had a median TSH value [3.9 mIU/L (0.5-13)] within normal range, but levels were high as compared to controls. Out of 6 children with SH, 3 were in partial remission, 3 were in complete remission. The TSH levels normalized on thyroxine supplementation in grades II and III subclinical hypothyroidism. CONCLUSION: Subclinical non-autoimmune hypothyroidism is present in a significant proportion of children with SRNS despite partial or complete remission. Thyroid profile should be evaluated routinely in this subset of patients.

Discrepancy in Fluid and Crystallized Intelligence: An Early Cognitive Marker of Dementia from the LASI-DAD Cohort.

Background: Cognitive aging is a complex phenomenon, which comprises various cognitive skills, broadly categorized into fluid and crystallized intelligence. Crystallized intelligence (gc) tends to be maintained, as opposed to fluid intelligence (gf), which tends to decline rapidly with age. The association of the two with cognitive decline remains a matter of conjecture requiring further research. Aim: The aim of the study was to identify the variables of gc and gf from a population data of Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study and investigate its relationship with the onset of cognitive impairment using discrepancy analysis against neuropsychological tests. Methods: This analysis of data from LASI-DAD study was carried out on a sample of 3,223 participants. They were assessed on extensive thirteen cognitive tests and one subjective test of cognition. Standardized score was used for discrepancy analysis. Fluid ability minus crystallized ability was used to assess the cognitive impairment. Any statistical significance with the score difference >0.99 SD was defined as a presence of cognitive decline. Hindi Mental Status Examination (HMSE) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were used as gold standard. Results: With increased discrepancy score, each cognitive parameter score declined which was found to be statistically significant. In HMSE (Normal = 25.81 ± 3.39; Impaired = 23.17 ± 3.54; p = <0.001), there was a drop of 2 point scores in identifying cognitive impairment in the population sample as per the gold standard. A similar trend was evident in other neurocognitive domains as well. Conclusion: Crystallized-fluid intelligence discrepancy analysis has a strong potential in predicting the onset of cognitive decline ahead of time, facilitating early intervention.

Endothelial dysfuntion in children with idiopathic nephrotic syndrome.

BACKGROUND: Impaired endothelial function is the initial step in atherogenesis, which is largely responsible for ischaemic heart disease and thrombotic strokes decades later. METHODS: Fourty two children with first episode nephrotic syndrome (FENS) aged 1-16 years and 40 controls were enrolled. Soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA), plasminogen activator inhibitor -1 (PAI-1) and von-willebrand factor (vWF) levels were measured in plasma in FENS, at 12 weeks of drug induced remission and in steroid resistant nephrotic syndrome (SRNS) patients at diagnosis. RESULTS: PAI-1, sTM, vWF and t-PA were significantly raised at the onset of nephrotic syndrome (p<0.0001). All the markers had a fall after 12 weeks of steroid treatment, but were still raised. Children with SRNS had higher levels of sTM, tPA, vWF as compared to infrequent relapsers, at onset and at 4 weeks of steroid treatment. CONCLUSION: Children with idiopathic nephrotic syndrome have endothelial dysfunction which is largely dependent upon disease activity.

Homocysteine metabolism in children with idiopathic nephrotic syndrome.

BACKGROUND: Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome. METHODS: Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1-16 years along with 30 age- and sex-matched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B12 and folic acid were measured with electro-chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B12 and folic acid in children with FENS, at 12 weeks and 1 year (remission). RESULTS: Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1-year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12-week and 1-year remission. CONCLUSION: Homocysteine metabolism is deranged in children with FENS. Renal effects of long-term raised urinary homocysteine levels need to be studied.

Incidence, clinical predictors and outcome of acute renal failure among North Indian trauma patients.

CONTEXT: There is a need for identifying risk factors aggravating development of acute renal failure after attaining trauma and defining new parameters for better assessment and management. Aim of the study was to determine the incidence of acute renal failure among trauma patients, and its correlation with various laboratory and clinical parameters recorded at the time of admission and in-hospital mortality. SUBJECTS AND METHODS: The retrospective cohort study included admitted 208 trauma patients over a period of one year. 135 trauma patients at the serum creatinine level >2.0 mg/dL were enrolled in under the group of acute renal failure. 73 patients who had normal creatinine level made the control group. They were further assessed with clinical details and laboratory investigations. RESULTS: Incidence of acute renal failure was 3.1%. There were 118 (87.4%) males and average length of stay was 9 (1, 83) days. Severity of injury (ISS, GCS) was relatively more among the renal failure group. Renal failure was transient in 35 (25.9%) patients. They had higher incidence of bone fracture (54.0%) (P= 0.04). Statistically significant association was observed between patients with head trauma and mortality 72 (59.0%) (P= 0.001). Prevalence of septic 24 (59.7%) and hemorrhagic 9 (7.4%) shock affected the renal failure group. CONCLUSION: Trauma patients at the urea level >50 mg/dL, ISS >24 on the first day of admission had 23 times and 7 times the risk of developing renal failure. Similarly, patients with hepatic dysfunction and pulmonary dysfunction were 12 times and 6 times. Patients who developed cardiovascular dysfunction, hematological dysfunction and post-trauma renal failure during the hospital stay had risk for mortality 29, 7 and 8 times, respectively. The final prognostic score obtained was: 14*hepatic dysfunction + 11*cISS + 18*cUrea + 12*cGlucose + 10*pulmonary dysfunction. Optimal score cut-off for prediction of renal failure was found to be ≥25 with specificity, sensitivity and positive likelihood ratio to be 84.9%, 78.4% and 3.9, respectively.