ORCID Profile
0000-0003-2128-7488
Current Organisation
Monash University
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Publisher: Elsevier BV
Date: 2015
DOI: 10.1038/KI.2014.240
Abstract: While studies show that prolonged initial prednisone therapy reduces the frequency of relapses in nephrotic syndrome, they lack power and have risk of bias. In order to examine the effect of prolonged therapy on frequency of relapses, we conducted a blinded, 1:1 randomized, placebo-controlled trial in 5 academic hospitals in India on 181 patients, 1-12 years old, with a first episode of steroid-sensitive nephrotic syndrome. Following 12 weeks of standard therapy, in random order, 92 patients received tapering prednisolone while 89 received matching-placebo on alternate days for the next 12 weeks. On intention-to-treat analyses, primary outcome of number of relapses at 1 year was 1.26 in the 6-month group and 1.54 in the 3-month group (difference -0.28 95% confidence interval (CI) -0.75, 0.19). Relative relapse rate for 6- vs. 3-month therapy, adjusted for gender, age, and time to initial remission, was 0.70 (95% CI 0.47-1.10). Similar proportions of patients had sustained remission, frequent relapses, and adverse effects due to steroids. Adjusted hazard ratios for first relapse and frequent relapses with prolonged therapy were 0.57 (95% CI, 0.36-1.07) and 1.01 (95% CI, 0.61-1.67), respectively. Thus, extending initial prednisolone treatment from 3 to 6 months does not influence the course of illness in children with nephrotic syndrome. These findings have implications for guiding the duration of therapy of nephrotic syndrome.
Publisher: Oxford University Press (OUP)
Date: 12-2020
DOI: 10.1093/CKJ/SFAA223
Publisher: Wiley
Date: 26-06-2022
DOI: 10.1111/NEP.14067
Abstract: Children with frequently relapsing (FR) or steroid dependent (SD) nephrotic syndrome (NS) often develop side effects of corticosteroids. Various steroid‐sparing agents are in practice, but only a few studies exist so far which have compared the safety and efficacy of these two commonly used agents. We did a retrospective medical records review of children with FRNS or SDNS who had levamisole or mycophenolate mofetil (MMF) as a steroid‐sparing agent with a minimum follow‐up period of 12 months. The aim was to compare the course of our patients on MMF and levamisole. Our primary objective was to determine the number of children in sustained remission and those with the infrequently relapsing course on levamisole and MMF and, the median time to relapse in months in the two groups. The secondary objective was to compare time to first relapse and number of relapses in FRNS and SDNS group children on MMF and levamisole. A total of 88 children (34% female) with diagnosis FR/SDNS (44 each) were included in the study. Thirty‐nine patients took levamisole, while 49 received MMF therapy. The median age of presentation at the relapsing course was 4.2 years. The proportion of children with sustained remission or infrequent relapsing (IFR) course on MMF was 73.6%, compared to 48.71% on levamisole ( p ‐value .015). In addition, the median time to first relapse was 12 months (24, 1.5) and 4.5 months (24, 1) on respective medications. Clinical outcome was superior in the MMF group than levamisole, especially in SDNS patients, and also MMF was more efficacious in maintaining sustained remission.
Publisher: Elsevier BV
Date: 2021
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000516911
Abstract: b i Background: /i /b Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in pathological proteinuria include congenital and acquired disorders, as well as both glomerular (immune/non-immune mediated) and tubular defects. b i Summary: /i /b Untreated proteinuria is strongly linked to progressive loss of kidney function and kidney failure. Excess protein reaching the renal tubules is ordinarily resorbed by the tubular epithelium. However, when these mechanisms are overwhelmed, a variety of inflammatory and fibrotic pathways are activated, causing both interstitial fibrosis and glomerulosclerosis. Nevertheless, the specific mechanisms underlying this are complex and remain incompletely understood. Recently, a number of treatments, in addition to angiotensin system blockade, have been shown to effectively slow the progression of proteinuric chronic kidney disease. However, additional therapies are clearly needed. b i Key message: /i /b This review provides an update on the pathophysiology of proteinuria, the pathways leading to fibrosis, and an overview of current and emerging therapies.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.NEFROE.2022.03.005
Abstract: The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.
Publisher: Oxford University Press (OUP)
Date: 13-04-2018
DOI: 10.1093/CKJ/SFY027
Publisher: Springer Science and Business Media LLC
Date: 18-03-2015
DOI: 10.1007/S12098-015-1743-1
Abstract: Information on provision of continuous renal replacement therapy (CRRT) in critically ill children from developing countries is limited. The authors describe their experience in 17 children with hypotension and acute kidney injury (AKI) with fluid overload or electrolyte imbalance managed by 20 sessions of CRRT. The median (range) age and weight were 6 y (0.75-18) and 20 kg (6.2-42), respectively. All patients were receiving inotropic agents nine had fluid overload (19 %, range 11-34.1 %) and ten had severe AKI. Median clearance and filter-life were 2171.4 ml/1.73 m(2)/h (1730.6-4405.8) and 69.7 h (2.8-98.3), respectively. Complications were catheter flow related (n = 1), filter clotting (n = 3), hemorrhage (n = 3), hypokalemia (n = 16) and hypophosphatemia (n = 11). Eight patients (47.1 %) survived the median PRISM III score of survivors was significantly lower than non survivors (10.5 vs.17.0 P 0.02). Renal function recovered in the survivors emphasizing the role of this modality in managing critically ill patients.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.NBD.2019.104524
Abstract: Tyrosine hydroxylase is the key enzyme controlling the synthesis of the catecholamines including dopamine. The breakdown of dopamine into toxic compounds has been suggested to have a key role in the degeneration of the dopaminergic neurons in Parkinson's disease. Humans are unique in containing four isoforms of tyrosine hydroxylase, but understanding of the role of these isoforms under normal conditions and in disease states is limited. The aim of this work was to determine the level and distribution of the four human isoforms in tissues from healthy controls and patients with Parkinson's disease. The results show that isoform 1 and isoform 2 are the major tyrosine hydroxylase isoforms in human brain, but that tyrosine hydroxylase isoform 2 is more abundant in the substantia nigra than the tyrosine hydroxylase isoform 1. The two minor isoforms, isoform 3 and isoform 4, are expressed at a proportionally higher level in the terminal field regions (caudate and putamen) compared to the substantia nigra. There was a selective loss of tyrosine hydroxylase isoform 1 in Parkinson's disease compared to age-matched controls and a corresponding increase in the proportion of tyrosine hydroxylase isoform 2. Phosphorylation of serine 40 was significantly increased in caudate, putamen and ventral tegmental area, but not in the substantia nigra, in Parkinson's disease brain. These results show a selective sparing of tyrosine hydroxylase isoform 2 in Parkinson's disease. Isoform 2 exhibits a reduced capacity for activation compared to isoform 1, which may account for the selective sparing of cells expressing isoform 2 in Parkinson's disease. Surviving neurons in Parkinson's disease brain exhibit a substantial increase in tyrosine hydroxylase phosphorylation consistent with a compensatory mechanism of increased dopamine synthesis in the terminal field regions.
Publisher: Elsevier BV
Date: 09-2020
Publisher: MDPI AG
Date: 03-12-2020
DOI: 10.3390/IJMS21239233
Abstract: The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.
Publisher: Medknow
Date: 04-2016
Publisher: Springer Science and Business Media LLC
Date: 09-05-2015
DOI: 10.1007/S10157-015-1119-X
Abstract: Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and hyperchloremic metabolic acidosis. It is important to understand that despite knowing the disease for 60-70 years, complexities in the laboratory tests and their interpretation still make clinicians cautious to diagnose and label types of tubular disorder. Hence, we are writing this mini-review to emphasize on the step wise approach to RTA with some understanding on its basic etiopathogenesis. This will definitely help to have an accurate interpretation of urine and blood reports in correlation with the clinical condition. RTA can be a primary or secondary defect and results either due to abnormality in bicarbonate ion absorption or hydrogen ion secretion. Primary defects are common in children due to gene mutation or idiopathic nature while secondary forms are more common in adults. We are focusing and explaining here in this review all the clinical and laboratory parameters which are essential for making the diagnosis of RTA and excluding the extrarenal causes of hyperchloremic, normal anion gap metabolic acidosis.
Publisher: Georg Thieme Verlag KG
Date: 29-07-2021
Abstract: Galactosialidosis (GS) is a rare lysosomal storage disorder. We reported here, the case of a 29-day-old boy who had increased body swelling, difficulty breathing, and petechiae on the trunk since birth. The antenatal history was unremarkable. Clinical laboratory findings included coarse facies, hepatosplenomegaly, gross ascites, thrombocytopenia, nephrotic range proteinuria, and bilateral hydronephrosis. The diagnostic challenge was resolved after genetic testing, which revealed GS with a novel homozygous c.1158dupA mutation.
Publisher: Wiley
Date: 11-07-2019
DOI: 10.1002/JCB.29279
Abstract: Tyrosine hydroxylase (TH) is the key enzyme that controls the rate of synthesis of the catecholamines. SH‐SY5Y cells with stable transfections of either human tyrosine hydroxylase isoform 1 (hTH1) or human tyrosine hydroxylase isoform 4 (hTH4) were used to determined the subcellular distribution of TH protein and phosphorylated TH, under basal conditions and after muscarine stimulation. Muscarine was previously shown to increase the phosphorylation of only serine 19 and serine 40 in hTH1 cells. Under basal conditions, the hTH1 and hTH4 proteins, their serine 19 phosphorylated forms and hTH1 phosphorylated at serine 40 were all similarly distributed with ~80% in the cytosolic fraction, ~20% in the membrane fraction, and less than 1%, or not detectable, in the nuclear fraction. However, hTH4 phosphorylated at serine 71 had a significantly different distribution with ~65% cytosolic and ~35% membrane associated. Muscarine stimulation led to hTH1 being redistributed from the cytosol and nuclear fractions to the membrane fraction and hTH4 being redistributed from the cytosol to the nuclear fraction. These muscarine stimulated redistributions were not due to TH phosphorylation at serine 19, serine 40, or serine 71 and were most likely due to TH binding to proteins whose phosphorylation was increased by muscarine. This is the first study to show a difference in subcellular distribution between two human TH isoforms under basal and stimulated conditions.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Georg Thieme Verlag KG
Date: 11-11-2019
Abstract: A 5-month-old female infant from a consanguineous Indian Muslim family presented with polyuria, polydipsia, failure to thrive, impaired renal function, and neonatal hepatitis of unknown cause at 1 month of age. Clinical exome testing revealed renal–hepatic–pancreatic dysplasia caused by homozygous c. 1985 + 5G A pathogenic variations in NPHP3. Our case illustrates delay in confirmatory diagnosis of such rare disorders in our region due to the lack of suspicion and unawareness of the availability of genetic testing even when there are no cost constraints.
No related grants have been discovered for Sonia Sharma.