Complications in paediatric liver transplant from Kuwait when transplanted abroad

Background and study aimsSince the introduction of liver transplantation (LTx) in children suffering from liver failure in 1963, many centres around the world have offered this service to children that have no other alternative. The aim of this retrospective study is to analyse the results of paediatric liver transplant in Kuwait over the last decade.Patients and methodsA retrospective chart review was done involving paediatric patients during the time period of 1995–2004. The information collected included patient demographics, indications for liver transplantation, survival of both patient and allograft, and complications.ResultsA total of 16 cases were found and analysed. The mean age was 3.6 years (ranged 5 months–17 years). There were nine boys and seven girls. The most common indications for LTx were biliary atresia and metabolic liver disease. All the liver transplants were done abroad. There were totally nine deceased donor and seven living related cases. The complications were acute cellular rejection in five, hypertension in two, biliary complications in four, cytomegalovirus (CMV) infection in three and post lymphoproliferative disease in two cases. All but one patient are presently alive.ConclusionThe above information demonstrates that LTx in Kuwati children is safe and improves the quality of life for those that would otherwise have no other alternative.     

Magnetic phase transition from paramagnetic in Nb2AlC-MAX to superconductivity-like diamagnetic in Nb2C-MXene: an experimental and computational analysis

Transition metal carbides (TMCs) have recently emerged as competent members among the family of two-dimensional (2D) materials, owing to their promising applications. There are many promising applications of MXenes; however, their magnetic properties lack a wide margin, both experimentally as well as theoretically, which needs to be investigated for potential use in spintronics. In this study, we carried out a comprehensive etching process via selective extraction of Al layers from Nb₂AlC-MAX using a wet electrochemical route under well-optimized conditions to obtain fine 2D-Nb₂C MXene sheets. Structural analysis using X-ray diffraction (XRD) confirms the effective removal of Al followed by confirmation of a 2D layered structure from morphological analysis using scanning electron microscopy (SEM). Zero-field-cooled (ZFC) and field-cooled (FC) measurements of MAX and MXene at different field strengths were performed using a superconducting quantum interference device (SQUID). Magnetic measurements reveal the paramagnetic nature of Nb₂AlC-MAX measured under 5 mT; however, this changes to a clear superconductor-like diamagnetic behavior with a shift of the magnetization from positive to negative values at low temperatures when measured under 5 mT and 10 mT for Nb₂C MXene. The diamagnetism, however, is changed to paramagnetism at 100 mT, which shows the existence of critical fields known typically for a type-II superconductor. To gain an insight into this unusual behavior in MXene, density functional theory (DFT) first-principles calculation was also performed in Wein2K software using spin-polarized generalized gradient approximation (sp-GGA). The magnetic moment of the compound is calculated to be negative, which corresponds well with the experimental finding and suggests that the negative magnetic moment originated from the d-orbital of Nb₂C. The present report provides a pathway to deeply understanding the existence of superconductivity-like diamagnetic behavior in Nb₂C MXene, which is useful for future magnetic applications.

Transition metal carbides (TMCs) have recently emerged as competent members among the family of two-dimensional (2D) materials, owing to their promising applications.

In two-dimensional (2D) materials, magnetism at the nanoscale is at the forefront of many cutting-edge technological applications, such as spintronic devices. Naguib et al. have synthesized a new class of two-dimensional materials, known as MXenes (M_nX_n+1), discovered in 2011, giving a possibility of magnetism in such 2D materials and their promising uses in spintronic devices.¹ These 2D layer structured early transition metal carbides and/or nitrides are known as MXenes, so named to indicate their structural similarities with graphene.² MXenes are derived from 3D MAX phases (space group P6₃/mmc) in which “M” is an early transition metal, e.g., Ti, Ta, V, etc.; “A” is mainly a group 13 or group 14 element (group III-A or IV-A), e.g., Si, Al; “X” is a carbide, nitride or can be both; and n = 1, 2, 3 represents the number of layers, forming 211, 312 and 413 phases.^3–5 Over the past decade, this new material has gained enormous attention, thus developing an entirely new research field to disclose the properties of the 2D state of this material. The materials in the 2D regime own a cluster of astonishing physical properties as compared to the 3D nature, but intrinsic two-dimensional magnetism has proved to be challenging. As 2D semiconductors have revamped the field of electronics, similarly, magnetism in 2D materials could remodel spintronic devices that can employ a spin degree of freedom.^6,7Nb₂C MXene was first synthesized by Naguib et al., but they just reported its electrochemical activity as a promising electrode material.⁴ Further work has been reported in Nb₂C with various biomedical applications, energy storage, supercapacitors, and nanoelectronics.^9–19 As far as the magnetism in such 2D MXenes is concerned, it remains less investigated, and this research void needs to be filled. Recently, Babar et al. reported the observation of superconductivity in as-prepared powdered Nb₂C for the first time, with the highest onset transition temperature T_c,onset = 12.5 K among the MXene family. However, the authors did not discuss the magnetic nature of the parent Nb₂AlC MAX itself and did not reason for the presence of unusual magnetic effects in MXene.⁸ MXenes are favorable members of 2D magnetism, and different magnetic natures are computationally predicted in various carbide and nitride MXenes.^7,20 The existence of novel room-temperature ferromagnetic order in doped MXene and the coexistence of different magnetic phases in MXene, along with experimental evidence, indicate its potential of hosting diverse magnetic natures.^21,22 Considerable research has been focused on these 2D structures due to their importance and favorable applications, such as spintronics. MXene could provide a vast platform for exploring the magnetic properties and is one of the best candidates that can host superconductivity as compared to other members of the 2D family. Experimental studies are generally dependent upon numerous variables, thus affecting the research pace. However, density functional theory-based first principles calculation and theoretical simulations are a successful way to examine and foresee the properties of low-dimensional materials. This provoked us to theoretically explore superconductivity in Nb₂C and their validation through superconductivity measurements of experimentally synthesized Nb₂C MXene. In this work, we report a systematic etching mechanism of Nb₂C MXene to obtain fine 2D sheets via a chemical etching route using hydrofluoric (HF) acid. Structural and morphological studies using the X-ray diffraction technique (XRD), scanning electron microscopy (SEM) and elemental analysis by energy-dispersive X-ray spectroscopy (EDX) show the effective removal of Al from the parent 3D-Nb₂AlC MAX, thus revealing an accordion-like sheet structure. Optical analysis indicates a significant reduction in bandgap after chemical etching. Magnetic properties were carried out to observe the signatures of superconductivity (a perfect diamagnetic state, negative magnetic moment) and its magnetic nature at room temperature. To study the magnetic nature of as-prepared powder-form Nb₂C, density functional theory (DFT) first principles calculation was carried out through Wein2K using spin-polarized generalized gradient approximation (sp-GGA). The magnetic moment of the compound is calculated to be −0.00485, which although but small is important, as the value is negative, which is an indication of the presence of diamagnetism in Nb₂C. Here, the detailed chemical etching process, magnetic properties of Nb₂AlC MAX and its effect on magnetic phase of Nb₂C MXene, and the density functional theory calculation are reported, which were not discussed by Babar et al. in ref. 8.     

Predictors of renal replacement therapy and mortality in children with chronic kidney disease

Objectives:

To study the epidemiology of chronic kidney disease (CKD) in children, and to look for risk factors to predict renal replacement therapy (RRT) and mortality.

Methods:

This is a retrospective cohort study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 2006 and 2014, where the files of 1,000 children with CKD were reviewed. We determined the effect of consanguinity and hypertension, and being a Saudi indigene on mortality and RRT. We compared children with congenital versus non-congenital causes of CKD.

Results:

The mean±standard deviation age at presentation was 4.9±4.3 years. The median duration of follow up was 1.5 (interquartile range [IQR]: 0.4-4.0) years. Only 9.7% of children received RRT, and 8.3% died. The underlying etiology for CKD was congenital in 537 children. The congenital CKD group presented at a younger age group (3.5±4.0 versus 6.6±3.9 years, p<0.0001), had more advanced stages of CKD (p<0.0001), higher rates of consanguinity (75.4% versus 47.1%, p<0.0001), and RRT (p<0.004) than children with non-congenital CKD. Risk factors for RRT among children with CKD include being a Saudi indigene (relative risk [RR]=1.49, 95% confidence interval (CI): 1.01-2.21), and hypertensive (RR=5.29, 95% CI: 3.54-7.91). The risk factor for mortality was hypertension (RR=2.46, 95% CI: 1.66-3.65).

Conclusion:

Congenital causes of CKD represent the main etiology of CKD in children living in the western province of Saudi Arabia. Significant risk factors for RRT include congenital CKD, Saudi nationality, and hypertension. Hypertension is also a predictor of mortality in children with CKD.Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health.1 Children with CKD who are on renal replacement therapy (RRT) have higher mortality rate, which is at least 30-fold higher than their age-matched peers.2 Epidemiological information on the incidence and prevalence of pediatric CKD in children is currently limited,3 particularly in developing countries. Furthermore, most of the available epidemiological data are from end-stage kidney disease (ESKD) registries, and information on the earlier stages of pediatric CKD is still lacking.4 The early stages of CKD in the pediatric population are in most cases asymptomatic, and are therefore under-diagnosed and under-reported.4 Direct comparisons of the incidence and prevalence rate of pediatric CKD are complex since each pediatric CKD registries uses different definition; some depend on the estimated glomerular filtration rate (eGFR), while others use serum creatinine levels. The incidence in Europe was consistent between 11-12 per million of the age-related population (pmarp) for CKD stages 3-5, and 8 pmarp for CKD stages 4-5.4 Data available on the exact prevalence of various kidney diseases in the Arab world is very limited. Most of the data come from small studies and are of limited generalizability.5 In Kuwait, the mean incidence was found to be as high as 38 pmarp, while the prevalence was as also high at 329 pmarp in 2003.6 An incidence of 11 pmarp and a prevalence of 51 pmarp has been reported in Jordanian children.7 The epidemiological data of CKD in children is very scarce in Saudi Arabia. One study from Asir reported that the mean annual incidence of CRF of 15.6 per million children, the mean annual incidence of ESRF is 9.2 per million children, and congenital anomalies of the urinary system constitute the most common cause of chronic renal failure (CRF).8 Another study from Jeddah reported similar results.9 All these studies enrolled a small number of children (less that 100). In the light of a limited data available regarding the epidemiology of CKD in children in Saudi Arabia, we performed a retrospective study to examine the risk factors for RRT and mortality among children with CKD.     

Social Impact of Dialysis on Children and Their Families

Objectives

To evaluate the social consequences of dialysis on children and their parents.

Methods

From January through June 2012 short structured interviews with parents or caregivers of children on peritoneal dialysis (PD) or hemodialysis (HD) who were followed up at King Abdulaziz University Hospital, King Faisal Specialty Hospital and Research Center, or the Kidney Center at King Fahad Hospital were conducted. Data were analyzed using the Statistical Package for the Social Sciences.

Results

Thirty six children (22 boys and 16 girls) and their families were included. The mean (SD) age of the children was 11.5?±?6.87 y, and the mean (SD) duration of dialysis was 28?±?11.32 mo. Only one third of the families had the opportunity to choose the modality of dialysis. Both modalities of dialysis had a negative effect on fathers’ jobs in over 50 % of the cases. Similarly, both modalities of treatment had a considerable impact on the quality of care provided by the mothers to other family members. There was no difference between the two modalities on the frequency of admissions.

Conclusions

Both PD and HD had a negative impact on fathers’ jobs and on the level of care provided by mothers to the rest of the family.     

Renal impairment in children with posterior urethral valves

Background

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

Methods

We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

Results

The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p?=?0.024), nadir serum creatinine (p?<?0.001), and last known serum creatinine level (p?=?0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p?=?0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

Conclusions

Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.     

Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/lpr mice model of arthritis and in humans. METHODS: In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints. RESULTS: At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice. CONCLUSIONS: These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.     

What is the calcineurin inhibitor of choice for pediatric renal transplantation?

Cyclosporine microemulsion (CyA) and tacrolimus (Tac) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. In the majority of patients, these calcineurin inhibitors have been used in combination with other immunosuppressive drugs, such as azathioprine or mycophenolate mofetil (MMF). In this review we will address the question of what calcineurin inhibitor we should use in an individual pediatric renal transplant patient. Well-designed randomized studies in children showed no difference in short-term patient and graft survival with cyclosporine microemulsion and tacrolimus. However Tac is significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population when used in conjunction with azathioprine and corticosteroids. This difference disappears when calcineurin inhibitors are used in combination with MMF as both Tac and CyA produce similar rejection rates and graft survival. However, Tac is associated with improved graft function at 1 and 2 yr post-transplant. Adverse events of hypomagnesaemia and diarrhea seem to be higher in Tac group whereas hypertrichosis, flu syndrome and gum hyperplasia occurs more frequently in the CyA group. The incidence of post-transplant diabetes mellitus was almost identical between Tac and CyA treated patients. The recommendation drawn from the available data is that both CyA and Tac can be used safely and effectively in children. However Tac may be preferable to CyA because of steroid sparing effect and less hirsutism. We recommend that cyclosporine should be chosen when patients experience Tac-related adverse events. Nevertheless, the best calcineurin inhibitor should be decided on individual patients according to variable risk factors, such as risk of rejection in sensitized patient or delayed graft function. The possibility of adverse events should also be considered.     

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium (Mg) and calcium (Ca) in the thick ascending limb of Henle's loop. We have studied seven Arab patients with this syndrome who belong to four different families. The mean age at first presentation was 1.5+/-1.3 years (range 0.1-3 years) and at diagnosis 5.9+/-4.3 years (range 0.5-12 years). The presenting features were convulsions and carpopedal spasms (5 patients), polydipsia and polyuria (2 patients), rickets (2 patients), and recurrent urinary tract infections (1 patient). Bilateral nephrocalcinosis was observed in all patients. All patients had hypomagnesemia with a mean serum Mg of 0.45+/-0.09 mmol/l, an inappropriately high urine Mg of 2.07+/-0.73 mmol/24 h or fractional excretion of 15.3+/-7.1%, high urine Ca excretion of 4.1+/-1.2 mmol/24 h or urine Ca to creatinine ratio of 2.6+/-1.6, and normal serum potassium level of 4.4+/-0.34 mmol/l. All patients received Mg supplements and thiazide but exhibited slow worsening of their kidney function. After a mean follow-up of 4.4+/-3.9 years, one patient progressed to end-stage renal failure (ESRF). In conclusion, we report seven Arab patients with FHHNC syndrome. The clinical and biochemical data were similar to previous reports. However, they tend to show a slower rate of progression to ESRF.