Exploring systemic inflammation in children with chronic kidney disease: correlates of interleukin 6.

BACKGROUND: Systemic inflammation (SI) is linked to chronic kidney disease (CKD) progression and multiple complications. Data regarding SI biomarkers in pediatric patients are scarce. This case-control and cross-sectional study investigates the correlation of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin to serum interleukin-6 (IL-6). METHODS: NLR and PLR were measured in 53 patients (median age: 12.9 years), including 17 on dialysis and 36 with a median glomerular filtration rate of 39 ml/min/1.73m2, and in 25 age and sex-matched healthy controls. Iron profile, serum albumin and IL-6 were measured in the patient group. IL-6 levels > 3rd quartile were classified as high. RESULTS: Patients presented higher NLR and PLR and particularly those on dialysis (p < 0.001 and p = 0.001). We observed a significant correlation between natural logarithm (ln) of IL-6 (lnIL-6) and NLR (rs = 0.344, p = 0.014), serum albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Combination of NLR, serum albumin and TIBC predicted high IL-6 (13 patients) with an AUC of 0.771 (95% CI 0.608-0.943). Pairing of NLR ≥ 1.7 and TIBC ≤ 300 µg/dL exhibited the highest sensitivity (76.9%), while incorporating serum albumin ≤ 3.8 g/dL along with them achieved the highest specificity (95%) for detecting high IL-6 levels. CONCLUSION: Both NLR and PLR levels increase in CKD, especially in patients on chronic dialysis. NLR, rather than PLR, along with TIBC and serum albumin, are associated with IL-6 in pediatric CKD.

Immunologic Response to SARS-CoV-2 Vaccination in Pediatric Kidney Transplant Recipients: A Systematic Review and Meta-Analysis.

The pediatric population is at a lower risk of severe SARS-CoV-2 infection compared to adults. Nevertheless, immunosuppression in pediatric and adolescent kidney transplant recipients (KTRs) increases their hazard compared to the general population. This systematic review evaluates the efficacy of SARS-CoV-2 vaccines and determines the risk factors of no seroconversion in this population. PubMed-MEDLINE databases were searched for cohort studies. A meta-analysis was performed using fixed and random effect models. In total, seven studies including 254 patients were further analyzed. The random effect model demonstrated a 63% seroconversion rate (95% CI 0.5, 0.76) following a two-dose schedule, which increased to 85% (95% CI 0.76, 0.93) after the third dose administration. Seropositivity was lower in patients under mycophenolate mofetil compared to azathioprine (OR 0.09, 95% CI 0.02, 0.43). Rituximab administration decreased the seroconversion rate (OR 0.12, 95% CI 0.03, 0.43). The glomerular filtration rate (GFR) was 9.25 mL/min/1.73 m2 lower (95% CI 16.37, 2.13) in patients with no seroconversion. The seroconversion rate was lower in vaccinated compared to infected patients (OR 0.13, 95% CI 0.02, 0.72). In conclusion, vaccination against SARS-CoV-2 in pediatric and adolescent KTRs elicits a humoral response, and a third dose is advised. Previous rituximab administration, antimetabolite therapy with mycophenolate mofetil and lower GFR reduce the likelihood for seroconversion.

Association Between Adipokine Profile, Systemic Inflammation, Muscle and Protein Energy Wasting in Children With Chronic Kidney Disease.

OBJECTIVES: This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD). METHODS: We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL. RESULTS: PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 µg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance. CONCLUSIONS: In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

Leclercia adecarboxylata in Peritoneal Dialysis Patients: A Systematic Review.

Background:Leclercia adecarboxylata is a Gram-negative bacillus that can rarely cause infections in humans. We recently treated a case of peritonitis due to L. adecarboxylata in a peritoneal dialysis (PD) pediatric patient, and we systematically reviewed all the relevant reported cases in the literature. Methods: We searched the PubMed and Scopus databases, and we reviewed 13 such cases (2 children, 11 adults) that were reported, including our patient. Results: The mean (±SE) age was 53.2 ± 22.5 years, with a male-to-female ratio of approximately 1:1.6. Their mean vintage period on PD prior to L. adecarboxylata peritonitis was 37.5 ± 25.3 months. The VITEK card was the identification diagnostic tool in most cases (63%). The antimicrobial agent that was most frequently used was ceftazidime, which was implemented in 50% of cases as initial therapy, either as a monotherapy or combination therapy; in only two patients (15.3%) was the Tenkhoff catheter removed. The median duration of treatment was 18 days (range of 10-21 days), and all 13 patients that were reviewed were healed. Conclusions: Physicians should be aware that L. adecarboxylata is noted to rarely cause peritonitis in PD patients; however, this pathogen seems to be sensitive to most antimicrobial agents and can result in a favorable outcome with the selection of appropriate treatment.

Fibroblast growth-factor 23 and vitamin D are associated with iron deficiency and anemia in children with chronic kidney disease.

BACKGROUND: This cross-sectional study investigates the association of fibroblast growth-factor 23 (FGF23) and other bone mineral parameters with iron status and anemia in pediatric chronic kidney disease (CKD). METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), intact parathormone, c-terminal FGF23, a-Klotho, iron (Fe), ferritin, unsaturated iron-binding capacity, and hemoglobin (Hb) were measured in 53 patients from 5 to 19 years old with GFR < 60 mL/min/1.73 m2. Transferrin saturation (TSAT) was calculated. RESULTS: Absolute (ferritin ≤ 100 ng/mL, TSAT ≤ 20%) and functional iron deficiency (ferritin > 100 ng/mL, TSAT ≤ 20%) were observed in 32% and 7.5% of patients, respectively. In CKD stages 3-4 (36 patients), lnFGF23 and 25(OH)D were correlated with Fe (rs = - 0.418, p = 0.012 and rs = 0.467, p = 0.005) and TSAT (rs = - 0.357, p = 0.035 and rs = 0.487, p = 0.003) but not to ferritin. In this patient group, lnFGF23 and 25(OH)D were correlated with Hb z-score (rs = - 0.649, p < 0.001 and rs = 0.358, p = 0.035). No correlation was detected between lnKlotho and iron parameters. In CKD stages 3-4, in multivariate backward logistic regression analysis, including bone mineral parameters, CKD stage, patient age, and daily alphacalcidol dose as covariates, lnFGF23 and 25(OH)D were associated with low TSΑΤ (15 patients) (OR 6.348, 95% CI 1.106-36.419, and OR 0.619, 95% CI 0.429-0.894, respectively); lnFGF23 was associated with low Hb (10 patients) (OR 5.747, 95% CI 1.270-26.005); while the association between 25(OH)D and low Hb did not reach statistical significance (OR 0.818, 95% CI 0.637-1.050). CONCLUSIONS: In pediatric CKD stages 3-4, iron deficiency and anemia are associated with increased FGF23, independently of Klotho. Vitamin D deficiency might contribute to iron deficiency in this population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Malnutrition Patterns in Children with Chronic Kidney Disease.

Malnutrition is frequent in children with chronic kidney disease (CKD). Apart from undernutrition and protein energy wasting (PEW), overnutrition prevalence is rising, resulting in fat mass accumulation. Sedentary behavior and unbalanced diet are the most important causal factors. Both underweight and obesity are linked to adverse outcomes regarding renal function, cardiometabolic risk and mortality rate. Muscle wasting is the cornerstone finding of PEW, preceding fat loss and may lead to fatigue, musculoskeletal decline and frailty. In addition, clinical data emphasize the growing occurrence of muscle mass and strength deficits in patients with fat mass accumulation, attributed to CKD-related wasting processes, reduced physical activity and possibly to obesity-induced inflammatory diseases, leading to sarcopenic obesity. Moreover, children with CKD are susceptible to abdominal obesity, resulting from high body fat distribution into the visceral abdomen compartment. Both sarcopenic and abdominal obesity are associated with increased cardiometabolic risk. This review analyzes the pathogenetic mechanisms, current trends and outcomes of malnutrition patterns in pediatric CKD. Moreover, it underlines the importance of body composition assessment for the nutritional evaluation and summarizes the advantages and limitations of the currently available techniques. Furthermore, it highlights the benefits of growth hormone therapy and physical activity on malnutrition management.

Fatigue and Quality of Life in Children with Chronic Kidney Disease.

Background: This study investigates the effect of chronic kidney disease (CKD) stage on fatigue and health-related quality of life (HRQoL) in the pediatric population. Material and Methods: The PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale (subcategories: general, sleep/rest, and cognitive fatigue) and HRQoL Generic Core Scales (subcategories: physical, emotional, social, and school functioning) questionnaires were completed by 30 patients aged from 7 to 18 years old with CKD stage 2−4, CKD stage 5 on dialysis (CKD 5D), and kidney transplantation (KTx), as well as their parents. Results: Both low "Total Fatigue" and "Total HRQoL" scores were reported in 16.7% of patients. "Sleep/Rest Fatigue", "Emotional Functioning", and "School functioning" were the lowest scored subcategories. CKD 5D/KTx patients presented lower "Sleep/Rest Fatigue" (p = 0.022) and, more frequently, low "School Functioning" scores (p = 0.029). The "Total HRQoL" score was correlated to the "Total Fatigue" score (rs = 0.625, p < 0.001). A low "Sleep/Rest Fatigue" score was associated with low "Physical Functioning", "School Functioning", and "Total HRQoL" scores (p = 0.016, p = 0.001, and p = 0.047 respectively). Parents' HRQoL score was lower than patients' score on "Physical Functioning" (p = 0.040) and "School Functioning" subcategories (p = 0.045). Conclusions: Fatigue and disturbed HRQoL are mostly observed in CKD 5D and KTx pediatric patients, and are associated with sleep disorders and school dysfunction. Fatigue affects HRQoL, which is perceived as more deteriorated by the patients' parents.

Impact of Metabolomics Technologies on the Assessment of Peritoneal Membrane Profiles in Peritoneal Dialysis Patients: A Systematic Review.

Peritoneal dialysis (PD) is an effective and frequent dialysis modality in adults, particularly preferred in infants and young children with end-stage renal disease (ESRD). Long-term exposure of the peritoneal membrane to dialysis solutions results in severe morphologic and functional alterations. Peritoneal dialysis effluent biomarkers are based on omics technologies, which could predict the onset or confirm the diagnosis of peritoneal membrane dysfunction, would allow the development of accurate early prognostic tools and, potentially, the identification of future therapeutic targets. The purpose of our study was to critically review the literature on the impact and the effectiveness of metabolomics technologies in peritoneal health. The main search was performed in electronic databases (PubMed/MEDLINE, Embase and Cochrane Central Register of Controlled Trials) from inception to December 2020, using various combinations of Medical Subject Headings (MeSH). The main search highlighted nine studies, of which seven were evaluated in detail. Metabolomics technologies may provide significant input in the recognition of peritoneal membrane dysfunction in PD patients and provide evidence of early intervention strategies that could protect peritoneum health and function.

Impact of de novo donor-specific HLA antibodies on pediatric kidney transplant prognosis in patients with acute declined or stable allograft function.

BACKGROUND: This retrospective multicenter long-term cohort study investigates de novo donor-specific HLA antibodies (dnDSA) impact on allograft survival in pediatric kidney transplantation (KTx), depending on allograft function at dnDSA detection. METHODS: Seventy patients with dnDSA screening in the context of acute allograft dysfunction (AAD) (>50% serum creatinine increase) or routine follow-up were included during a 20-year period. Number of dnDSA specificities and HLA total mean fluorescence intensity (MFI-sum) were collected. RESULTS: Median follow-up time was 8.6 years. Among the 22 dnDSA+ patients, 8 patients presented AAD. Compared with dnDSA- patients, allograft survival was shorter only in dnDSA+/AAD+ patients, regardless of dnDSA detection during the 5-year post-transplant period (9 patients) or later (13 patients) (log rank p < .001 and p < .001, respectively). One dnDSA+/AAD-, 7 dnDSA+/AAD+, and 5 dnDSA- patients lost their allograft. Allograft survival was shorter in dnDSA+/AAD+ patients compared with the 16 dnDSA-/AAD+ patients (log rank p < .001) but did not differ between dnDSA+/AAD- and dnDSA-/AAD- patients (log rank p = .157). dnDSA+/AAD+ and dnDSA-/AAD+ patients presented higher risk of allograft failure compared with the other patient groups after adjustment for recipient age at KTx, donor type, and incidence of delayed graft function (HR 11.322, 95% CI 3.094-41.429, p < .001). Concurrent MFI-sum >10 000 and multiple dnDSA specificities were more significantly associated with AAD, compared with each factor separately (p < .001). CONCLUSIONS: In pediatric KTx, AAD shortens allograft survival in dnDSA+ patients, regardless of dnDSA time detection, and is commonly observed when high MFI-sum concurs with multiple dnDSA specificities. dnDSA without AAD incidence does not determinately affect allograft survival.

Surgical management of Encapsulating Peritoneal Sclerosis (EPS) in children: international case series and literature review.

BACKGROUND: Encapsulating Peritoneal Sclerosis (EPS) is a rare phenomenon in paediatric patients with kidney failure treated with peritoneal dialysis (PD). This study highlights clinical challenges in the management of EPS, with particular emphasis on peri-operative considerations and surgical technique. METHODS: Retrospective analysis of all paediatric patients with EPS treated at the Manchester Centre for Transplantation. RESULTS: Four patients were included with a median duration of 78 months on PD. All patients had recurrent peritonitis (> 3 episodes), and all had symptoms within three months of a change of dialysis modality from PD to haemodialysis or transplant. In Manchester, care was delivered by a multi-disciplinary team, including surgeons delivering the adult EPS surgical service with a particular focus on nutritional optimisation, sepsis control, and wound management. The surgery involved laparotomy, lavage, and enterolysis of the small bowel + / - stoma formation, depending on intra-abdominal contamination. Two patients had a formal stoma, which were reversed at three and six months, respectively. Two patients underwent primary closure of the abdomen, whereas two patients had re-look procedures at 48 h with secondary closure. One patient had a post-operative wound infection, which was managed medically. One patient's stoma became detached, leading to an intra-abdominal collection requiring re-laparotomy. The median length of stay was 25 days, and patients were discharged once enteral feeding was established. All patients remained free of recurrence with normal gut function and currently two out of four have functioning transplants. CONCLUSIONS: This series demonstrates 100% survival and parenteral feed independence following EPS surgery. Post-operative morbidity was common; however, with individualised experience-based decision-making and relevant additional interventions, patients made full recoveries. Health and development post-surgery continued, allowing the potential for transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Update on the Crosstalk Between Adipose Tissue and Mineral Balance in General Population and Chronic Kidney Disease.

Adipose tissue is nowadays considered as a major endocrine organ, which apart from controlling lipid metabolism, displays a significant role in energy expenditure, food intake and in the regulation of various systemic physiological processes. Adipose derived pro-inflammatory cytokines and adipokines, particularly leptin and adiponectin, provide inter-communication of adipose tissue with various metabolic pathways, ultimately resulting in a complex network of interconnected organ systems. Recent clinical and experimental research has been focused on exploring the direct interaction between adipokine profile and elements of mineral metabolism, including parathormone (PTH), fibroblast growth factor-23 (FGF23) and calcitriol. The emerging crosstalk between adipose tissue and calcium and phosphorus homeostasis suggests that metabolic disorders from one system may directly affect the other and vice versa. It is current knowledge that fat metabolism disturbance, commonly encountered in obese individuals, influences the expression of calciotriopic hormones in general population, while various clinical trials attempting to successfully achieve body fat loss by modulating mineral profile have been published. In chronic kidney disease (CKD) state, there is an increasing evidence suggesting that mineral disorders, influence adipose tissue and linked endocrine function. On the contrary, the impact of disturbed fat metabolism on CKD related mineral disorders has been also evocated in clinical studies. Recognizing the pathogenetic mechanisms of communication between adipose tissue and mineral balance is critical for understanding the effects of metabolic perturbations from the one system to the other and for identifying possible therapeutic targets in case of disrupted homeostasis in one of the two connected systems. To that end, this review aims to enlighten the recent advances regarding the interplay between mineral metabolism, fat mass and adipokine profile, based on in vitro, in vivo and clinical studies, in general population and in the course of CKD.

Association Between Secondary Hyperparathyroidism and Body Composition in Pediatric Patients With Moderate and Advanced Chronic Kidney Disease.

Objective: This single center cross-sectional study aims to investigate the association between secondary hyperparathyroidism and body composition in pediatric patients with moderate (stage 3) and advanced (stage 4-5) chronic kidney disease (CKD). Methods: 61 patients (median age: 13.4 years) were included. Body composition indices, including lean tissue index (LTI) and fat tissue index (FTI), were measured using multi-frequency bio-impedance spectroscopy. Muscle wasting was defined as LTI adjusted to height-age (HA) z-score < -1.65 SD and high adiposity as FTI z-score > 1.65 SD. Serum mineral metabolism parameters, including serum intact parathormone (iPTH), calcium, phosphorus and 25-hydroxyvitamin D, as well as serum leptin were measured in each patient. In advanced CKD patients, the mean values of serum mineral laboratory parameters of the 6 months prior to body composition assessment were recorded, and alfacalcidol index, defined as weekly alfacalcidol dose (mcg/week) per pg/ml of iPTH × 1,000, was calculated. Results: In moderate CKD (31 patients), high iPTH (>90 ng/ml) was observed in 10 (32.3%) patients and was associated with higher FTI z-score (p = 0.022). Moreover, serum iPTH was negatively correlated to LTI HA z-score (rs = -0.486, p = 0.006), and positively correlated to serum leptin levels (rs = 0.369, p = 0.041). The positive correlation between FTI z-score and iPTH (rs = 0.393, p = 0.039) lost significance after adjustment for serum leptin. iPTH was positively associated with high adiposity (12 patients, 38.7%) after adjustment for the other mineral metabolism parameters (OR 1.023, 95% CI 1.002-1.045, p = 0.028). In advanced CKD (30 patients), no significant correlation was observed between iPTH and body composition indices and serum leptin levels. Eleven (36.7%) patients with muscle wasting presented lower alfacalcidol index (p = 0.017). Alfacalcidol index ≤ 24 was strongly associated with muscle wasting after adjustment for CKD stage and other mineral metabolism parameters (OR 7.226, 95% CI 1.150-45.384, p = 0.035). Conclusion: Secondary hyperparathyroidism is associated with high adiposity in moderate but not in advanced CKD, with leptin acting as a potential contributive factor. In advanced CKD, targeting higher alfacalcidol weekly dose per each unit of serum PTH seems beneficial for preventing muscle wasting.

Poly(l-Lactic Acid)-co-poly(Butylene Adipate) New Block Copolymers for the Preparation of Drug-Loaded Long Acting Injectable Microparticles.

The present study evaluates the use of newly synthesized poly(l-lactic acid)-co-poly(butylene adipate) (PLA/PBAd) block copolymers as microcarriers for the preparation of aripiprazole (ARI)-loaded long acting injectable (LAI) formulations. The effect of various PLA to PBAd ratios (95/5, 90/10, 75/25 and 50/50 w/w) on the enzymatic hydrolysis of the copolymers showed increasing erosion rates by increasing the PBAd content, while cytotoxicity studies revealed non-toxicity for all prepared biomaterials. SEM images showed the formation of well-shaped, spherical MPs with a smooth exterior surface and no particle's agglomeration, while DSC and pXRD data revealed that the presence of PBAd in the copolymers favors the amorphization of ARI. FTIR spectroscopy showed the formation of new ester bonds between the PLA and PBAd parts, while analysis of the MP formulations showed no molecular drug-polyester matrix interactions. In vitro dissolution studies suggested a highly tunable biphasic extended release, for up to 30 days, indicating the potential of the synthesized copolymers to act as promising LAI formulations, which will maintain a continuous therapeutic level for an extended time period. Lastly, several empirical and mechanistic models were also tested, with respect to their ability to fit the experimental release data.

Subcutaneous Fat Necrosis and Hypercalcemia with Nephrocalcinosis in Infancy: Case Report and Review of the Literature.

Subcutaneous fat necrosis is an uncommon benign panniculitis affecting more commonly full-term newborns. It has been associated with birth asphyxia and meconium aspiration, as well as therapeutic hypothermia. Although the prognosis is generally favorable, complications such as hypercalcemia, thrombocytopenia, hypoglycemia and hypertriglyceridemia may complicate its course. The most serious complication is hypercalcemia that may reach life threatening levels and can be associated with nephrocalcinosis. We thereby describe a case of subcutaneous fat necrosis after therapeutic hypothermia, which presented with late-onset refractory severe hypercalcemia and persistent nephrocalcinosis during the follow up of the patient. Due to the risk of the development of chronic kidney disease, we highlight the importance of careful monitoring of hypercalcemia and review the literature of subcutaneous fat necrosis related to nephrocalcinosis.

Association between insulin growth factor-1, bone mineral density, and frailty phenotype in children with chronic kidney disease.

BACKGROUND: This cohort study investigates the association between insulin growth factor-1 (IGF-1), bone mineral density, and frailty phenotype in children with chronic kidney disease (CKD). METHODS: Forty-six patients (median age 14.5 years) were prospectively enrolled. Frailty phenotype was defined as the presence ≥ 3 of the following indicators: suboptimal growth/weight gain (body mass index height age < 5th percentile or height < 3rd percentile or loss of ≥ 10 percentiles/year in at least one parameter), low muscle mass (lean tissue mass height age < 5th percentile or loss of ≥ 10 percentiles/year), general fatigue reported by parent or child, and C-reactive protein > 3 mg/l. Lumbar bone mineral apparent density (LBMAD) was measured by dual-energy X-ray absorptiometry, body composition by bioimpedance spectroscopy, and IGF-1 by enzyme-labeled chemiluminescent immunometric assay. RESULTS: Frailty phenotype (seven patients) was more frequent in advanced CKD (estimated glomerular filtration rate < 30 ml/min/1.73m2) (p = 0.014). IGF-1 and LBMAD z-scores were lower in patients with suboptimal growth/weight gain (14 patients) (p = 0.013, p = 0.012), low muscle mass (nine patients) (p = 0.001, p = 0.009), and general fatigue (eight patients) (p < 0.001, p = 0.004). IFG-1 and LBMAD z-scores were associated with frailty phenotype (OR 0.109, 95% CI 0.015-0.798 and OR 0.277, 95% CI 0.085-0.903) after adjustment for CKD stage. IGF-1 z-score was associated with LBMAD < 5th percentile (six patients) (OR 0.020, 95% CI 0.001-0.450) after adjustment for CKD stage. The association between LBMAD and frailty phenotype lost significance after adjustment for IGF-1. CONCLUSION: Frailty phenotype is more frequent in advanced pediatric CKD. IGF-1 is negatively associated with frailty phenotype and interferes in the association between frailty and LBMAD.

Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review.

Methylmalonic acidemia and homocystinuria cobalamin C (cblC) type is the most common inborn error of the intracellular cobalamin metabolism, associated with multisystem involvement and high mortality rates, especially in the early-onset form of the disease. Hemolytic uremic syndrome (HUS) is a rare manifestation and needs to be distinguished from other causes of renal thrombotic microangiopathy. We describe a case of a 3-month-old infant, with failure to thrive, hypotonia and pallor, who developed HUS in the setting of cblC deficit, along with dilated cardiomyopathy, and presented delayed response to optic stimulation in visual evoked potentials, as well as enlarged bilateral subarachnoid spaces and delayed myelination in brain magnetic resonance imaging. Renal damage was reversed, while neurodevelopmental profile and eye contact improved after supplementation with parenteral hydroxycobalamin, oral folic acid, betaine and levocarnitine. Homozygous mutation of c.271dupA in the MMACHC gene was ultimately detected. In this report, we highlight the diagnostic challenges as well as the significance of early recognition and multidisciplinary management of this unusual condition. A brief review of published case reports of early-onset cblC deficit and related HUS is depicted, pointing out the initial clinical presentation, signs of renal damage and outcome, MMACHC gene type of mutations and accompanying extra-renal manifestations.

Muscle-bone axis in children with chronic kidney disease: current knowledge and future perspectives.

Bone and muscle tissue are developed hand-in-hand during childhood and adolescence and interact through mechanical loads and biochemical pathways forming the musculoskeletal system. Chronic kidney disease (CKD) is widely considered as both a bone and muscle-weakening disease, eventually leading to frailty phenotype, with detrimental effects on overall morbidity. CKD also interferes in the biomechanical communication between two tissues. Pathogenetic mechanisms including systemic inflammation, anorexia, physical inactivity, vitamin D deficiency and secondary hyperparathyroidism, metabolic acidosis, impaired growth hormone/insulin growth factor 1 axis, insulin resistance, and activation of renin-angiotensin system are incriminated for longitudinal uncoordinated loss of bone mineral content, bone strength, muscle mass, and muscle strength, leading to mechanical impairment of the functional muscle-bone unit. At the same time, CKD may also interfere in the biochemical crosstalk between the two organs, through inhibiting or stimulating the expression of certain osteokines and myokines. This review focuses on presenting current knowledge, according to in vitro, in vivo, and clinical studies, concerning the pathogenetic pathways involved in the muscle-bone axis, and suggests approaches aimed at preventing bone loss and muscle wasting in the pediatric population. Novel therapeutic targets for preserving musculoskeletal health in the context of CKD are also discussed.