Evaluation of Tubular Dysfunction Using Urine Biomarkers in Children with COVID-19.

OBJECTIVE: The coronavirus disease pandemic is a major problem that the world has been facing since December 2019. It mainly affects the respiratory system; however, the disease can affect the kidneys to different degrees. This study aimed to determine the changes in tubular dysfunction and inflammation parameters in children with coronavirus disease using urine biomarkers. MATERIALS AND METHODS: We included 36 children who tested positive for severe acute respiratory syndrome coronavirus 2 on real-time reverse transcriptase-polymerase chain reaction using respiratory specimens. Coronavirus disease-positive and -negative period parameters were evaluated. For measurement of interleukin-1ß, interleukin-6, and urine ß2 microglobulin levels, patients' urine samples were collected at diagnosis and 1 month after discharge. Additionally, routine urine and hematological parameters were evaluated concurrently. RESULTS: For all patients, the median urine ß2 microglobulin, serum urea, and lactate dehydrogenase levels were significantly higher in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). Further, serum platelet count was significantly lower in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). However, there was no difference in serum creatinine, interleukin-6, or interleukin-1ß levels between the 2 periods (P > .05). CONCLUSION: Our results suggest kidney involvement and tubular dysfunction in patients with asymptomatic, mild, and moderate infections. Furthermore, interleukin-1ß and interleukin-6 levels were high in the urine, even in non-critically ill patients. We believe that these findings contribute to the accumulation of evidence on continued inflammation in the kidney.

Urine analysis using FTIR spectroscopy: A study on healthy adults and children.

Urine spectra from 108 healthy volunteers are studied by attenuated total refraction-Fourier transform infrared (ATR-FTIR) spectroscopy. The spectral features are correlated with observable urine components. The variation of spectra within a healthy population is quantified and a library of reference spectra is constructed. Using the band assignments, these spectra are compared with both age-wise and gender-wise. Children show the least intensity variations compared to both adult groups. Young adults show the highest variation, particularly in the 1650 to 1400 cm-1 and 1200 to 900 cm-1 regions. These results indicate the importance of the size of the control group in comparative studies utilizing FTIR. Age-wise comparisons reveal that phosphate and sulfate excretion decreases with age, and that the variance of phosphate among individuals is higher with adults. As for gender-wise comparisons, females show a slightly higher citrate content at 1390 cm-1 regardless of the age and they show a higher variance in the 1200 to 1000 cm-1 region when compared to men.

Evaluation of urinalysis and urine culture in children with first-time urinary tract infection.

OBJECTIVE: This study aimed to review results of urinalysis with flow cytometry technique at the time of diagnosis of urinary tact infection (UTI), and to determine uropathogenes with their antibiotic resistance patterns in children with first-time UTI. MATERIAL AND METHODS: This single-centered, retrospective, cross-sectional study was conducted from January 2015 to December 2017. The study included 361 children with a first-time UTI diagnosis. Age, gender, results of automated urinalysis, urine culture results were recorded. RESULTS: Mean ages of children were 55.8±50.7 months. E. coli was the most common isolated microorganism followed by K. pneumoniae, Proteus, Enterococcus, and P. aeroginosa. Median count of pyuria was 44 leukocyte/mm3 (range:0-2954/mm3). Median count of pyuria in female and male patients were 53 and 22 leukocyte/mm3, respectively (p=0047). A total of 98 patients (27.1%) had no pyuria. Proportion of pyuria in female and male patients were 81.2% and 76%, respectively (p>0.05). Mean age of patients with and without pyuria were 59±52 months and 46±44months, respectively (p<0.05). According to uropathogen, there was pyuria at the ratio of 60% in Pseudomonas, 62.5% in Enterococcus spp, 66.7% in Proteus, 78.3% in Klebsiella, and 82.7% in E. coli. Children with UTI induced by E. coli had resistance ratios of 30.5% and 22.4% to cefixime and ceftiaxone, respectively. Children with UTI by Klebsiella spp had resistance ratios of 47.8% and 39.1% to cefixime and ceftriaxone, respectively. CONCLUSION: E. coli was the most common uropathogen in children with first-time UTI. Pyuria may be lacking according to age, gender, and type of uropathogene. Pyuria level was higher in females. In addition, ceftriaxone and cefixime resistance is increasing making ampirical treatment choices limited.

Magnesium excretion and hypomagnesemia in pediatric renal transplant recipients.

BACKGROUND: We investigated magnesium excretion and rate of hypomagnesemia in pediatric renal transplant recipients. METHOD: The medical records of 114 pediatric renal transplant recipients were retrospectively evaluated. After exclusion of 23 patients, 91 patients were included in the study. We recorded serum magnesium levels at the time of measurement of urine magnesium wasting. RESULTS: Mean serum magnesium levels were 1.73 ± 0.22 mg/dL and 38 of the patients (41%) had hypomagnesemia. There was a negative correlation between serum magnesium levels and estimated glomerular filtration rate and serum tacrolimus trough level (r=-0.215, p=0.040 and r=-0.409, p=0.000, respectively). Also, there was a statistically significant positive correlation between serum magnesium levels and transplantation duration (r=0.249, p=0.017). Mean fractional magnesium excretion was 5.9 ± 3.7% and 59 patients (65%) had high magnesium excretion. There was a significant negative correlation between fractional magnesium excretion and estimated glomerular filtration rate (r=-0.432, p=0.001). There was a significant positive correlation between fractional magnesium excretion and serum creatinine (r=0.379 p=0.003). CONCLUSION: Patients with higher tacrolimus trough blood levels, lower glomerular filtration rate and at early posttransplant period had risk of hypomagnesemia.

Association between vitamin D deficiency and disease activity in juvenile idiopathic arthritis.

Vitamin D has been shown to have immunomodulatory and anti-inflammatory properties in addition to its well-established role in the maintenance of mineral homeostasis and bone health. The aims of this study were to evaluate vitamin D status in patients with juvenile idiopathic arthritis (JIA), and also to examine whether there is an association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in JIA. Children with JIA who had an outpatient visit between March and April 2011 were evaluated retrospectively. Clinical and laboratory findings and vitamin D levels were evaluated. Disease activity was calculated using JADAS-27. Serum vitamin D levels were measured using high-performance liquid chromatography (HPLC). A total of 47 patients, 29 (61.7%) of them girls, with a mean age of 9.3±3.9 years and a median follow-up period of 28 months, were included in the study. The mean serum vitamin D level of all patients was 17.7±11.6 ng/ml. Vitamin D insufficiency (serum vitamin D: 15-20 ng/ml) and deficiency (serum vitamin D level <15 ng/ml) were found in 9 (19.1%) and 25 patients (53.2%), respectively. The vitamin D level was <20 ng/ml in 72.3% of the children. Only 13 patients (27.7%) were found to have adequate vitamin D levels (>20 ng/ml). There was a significant negative correlation between vitamin D levels and disease activity (p=0.01, r=-0,37). The mean JADAS-27 score was significantly higher in patients with 25(OH)D levels <15 ng/ml than in patients with 25(OH)D levels >15 ng/ml (p = 0.003). We suggest that vitamin D deficiency may be a possible modifiable risk factor affecting disease activity in JIA.

Hyperuricemia in pediatric renal transplant recipients.

OBJECTIVES: We sought to evaluate the prevalence and confounding clinical variables of hyperuricemia in pediatric kidney transplant patients. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 151 pediatric renal transplant recipients who received their grafts at Akdeniz University Medical Faculty in Antalya, Turkey, with a follow-up longer than 6 months. This retrospective, single-center study included 117 pediatric renal transplant recipients, after we had excluded the patients with changes in immunosuppressive treatment and graft loss, who were receiving therapy with allopurinol and furosemide. Patient information and laboratory data were obtained from patient charts and an electronic hospital database. RESULTS: Mean uric acid levels of patients were 311 ± 74 µmol/L, and 24 of all of the patients (20%) had high uric acid levels. Fifteen patients taking tacrolimus (16%), and 9 of patients taking cyclosporine (39%) had hyperuricemia. The hyperuricemia rate of patients taking cyclosporine was significantly higher than it was for those patients taking tacrolimus (P = .014). Mean levels of uric acid in patients taking cyclosporine were higher than those of patients taking tacrolimus (344 ± 62 µmol/L and 303 ± 75 µmol/L; P = .006). There was a significant positive correlation between mean uric acid concentrations, and both serum creatinine (P = .000; r=0.487) and cystatin C (P = .000; r=0.433). There was negative correlation between mean uric acid concentration and estimated glomerular filtration rate (P = .000; r=-0.417). Mean uric acid levels of patients with intact graft function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m²) was lower than the patients with a low estimated glomerular filtration rate (291 ± 67 µmol/L and 353 ± 71 µmol/L; P = .000). Mean uric acid level of patients with normal body mass index was significantly lower than that of patients who were obese-overweight (301 ± 64 µmol/L vs 343 ± 94 µmol/L; P = .045). CONCLUSIONS: We found 20% of our patient group had high uric acid levels. We also found that lower glomerular filtration rate, higher serum creatinine, cystatin c, obesity, and being overweight were risk factors for hyperuricemia in pediatric renal transplant recipients.

[BK virus infections in pediatric kidney transplant recipients]. / Pediatrik renal transplant alicilarinda BK virus enfeksiyonlari

Primary BK virus (BKV) infections acquired mainly during childhood are usually asymptomatic. Several studies revealed its seroprevalence in adult population as high as 90% worldwide. Following primary infection, virus persists as latent infection in the urogenital tract. In renal transplant recipients, primary infection and reactivations affect 10% of patients and without treatment, more than half of these patients lose their grafts. The only way of preventing graft loss due to BKV nephropathy (BKVN), seems to monitor BKV infection after transplantation and to diagnose patients developing BKVN during the early period and treat them accordingly. In this study, we analyzed BKV presence in plasma and urine samples with real-time PCR method and evaluated the renal biopsies of pediatric renal transplant recipients after transplantation, retrospectively. A total of 142 children (63 female, 79 male; mean age: 11.7 ± 3.9 years) who had renal transplantation in Akdeniz University Medical Faculty, Antalya, Turkey, between February 2006 and April 2011 were enrolled in the study. After transplantation, peripheral blood and urine samples were collected bi-weekly for the first three months, monthly till the sixth month and every three months thereafter. BKV DNA was additionally screened in patients with unexplained rise in serum creatinine or in patients receiving anti-rejection therapy. In any plasma positivity or during the BKVN therapy, BKV DNA analysis was done bi-weekly. After DNA extraction by automated system, an 83 base pair fragment in VP1 region was amplified. Signal detection for the target region was performed with a TaqMan probe dual-labelled at the 5' end with 6-carboxyfluorescein (FAM) and the 3' end with 6-carboxytetramethylrhodamine (TAMRA). Histopathological examinations of renal biopsies were done with routine histological stains and immunohistochemical staining with monoclonal antibodies directed to SV40 antigen. From 2171 plasma and 1995 urine samples without PCR inhibitors, 442 (20%) (range: 300-4.5 x 10(7) copies/ml; mean: 2.0 x 10(5) ± 2.2 x 10(6) copies/ml) and 800 (40.1%) (range: 300-3 x 10(12) copies/ml; mean: 5.9 x 10(9) ± 1.1 x 10(11) copies/ml) were found positive for BKV DNA, respectively. For 114 (80.3%) patients, at least one urine sample was positive and more than half of those patients (68/114, 59.6%) had viremia. Of the patients, 19.7% (28/142) had viral DNA above 10(4) copies/ml, which was choosen as a cut-off value for its high positive predictive value for BKVN. For all these 28 patients, prior to renal biopsy, immunosupressive treatment was decreased. Cidofovir and/or leflunomid were initiated to nine patients who did not respond to lowered immunosupressive therapy and eight of them had renal biopsy for the confirmation of BKVN. All renal biopsy results were compatible with BKVN. From these nine patients who were receiving cidofovir and/or leflunomid, two lost their grafts because of BKVN. Since viruria is frequently encountered and the viral load is usually in low quantities and transient, it is more appropriate to use blood samples for screening programmes after renal transplantation. The efficacy of antiviral treatment in BKVN could not be evaluated since it was only applied in patients non-responding to lowered immunosuppressive therapy and had decreased renal functions. Multicenter prospective studies are required to enlighten this important issue. Early diagnosis with close monitoring of renal function and viremia, seems to be the most effective way for controlling BKVN.

Renal function and linear growth of children with nephrocalcinosis: a retrospective single-center study.

The aim of this study was to analyze the etiology of nephrocalcinosis (NC) and whether it has any effect on growth and renal function in children. Forty-three children who were diagnosed with bilateral NC were studied retrospectively. Two neonates treated with furosemide and five premature infants were excluded from the study. The most common condition leading to NC was hereditary tubulopathies (50%). Data of 27 children who had a follow-up period of at least two years were examined in more detail. Of the 27 patients, the median age at first examination was 12 (range: 2-132) months and median follow-up time was 57 (range: 24-209) months. Thirteen of 27 (48.1%) patients had height standard deviation scores (hSDS) <-2 at presentation, and 6 (22.2%) patients who had normal glomerular function were still below -2 SDS at the last examination. Hypercalciuria was present in 25 (92.6%) patients at the first evaluation and in 6 (22.2%) patients at the last examination. The degree of NC worsened in 6 (22.2%), remained stable in 15 (55.5%) and decreased in 6 (22.2%) patients during the followup period. Chronic renal insufficiency (CRI) developed in 5 patients without there being any increase in the degree of NC. In conclusion, growth and renal function in these patients generally depend on the nature of the underlying disease but not the degree of NC.

Atypical hemolytic uremic syndrome due to factor H autoantibody.

Atypical hemolytic uremic syndrome (aHUS) is a disease caused by pathologies in the alternative complement system. The prevalence of aHUS is 10% of all aHUS cases. The subgroup of aHUS designated as DEAP (DEficiency of CFHR Proteins and CFH Autoantibody Positive)-HUS because of autoantibody to complement factor H (CFH) and CFH-related protein deficiency is seen very rarely, and the prevalence is 6% of all aHUS cases in the literature. We present here a female patient with DEAP-HUS. A 7.5-year-old girl with recurrent attacks of HUS had low C3 level. We initiated plasmapheresis treatment. After further analysis of the complement system, the result was compatible with DEAP-HUS, so we initiated immunosuppressive treatment. There were also family members with deficiency of CFHR-1 and CFHR-3, but they had no CFH autoantibody and no symptoms of HUS. In atypical cases of HUS, we should investigate complement status, especially for factor H autoantibody, for which treatment options differ from those of the other types of aHUS.

Effect of renal graft on longitudinal growth in prepubertal children.

OBJECTIVES: Linear growth impairment frequently accompanies chronic kidney disease in children. Despite successful renal transplant, growth retardation may persist in renal allograft recipients. MATERIALS AND METHODS: We recorded the longitudinal growth and biochemical data of prepubertal children during the first 2 years after renal transplant in 34 children (18 boys [52.9%]; mean age at renal transplant, 7.3 ± 2.5 y; range, 1.4 to 9.8 y). Height standard deviation scores were calculated. The patients were divided into 2 groups according to the increase in height standard deviation scores over the first 2 years after renal transplant: group 1 (increases in height standard deviation scores < 1) and group 2 (increases in height standard deviation scores > 1). RESULTS: Increases in height standard deviation scores were 0.12 ± 0.34 and 1.62 ± 0.52 for group 1 and group 2 (P < .001). The number of acute rejection episodes was significantly different between groups (P = .04). At renal transplant, increases in height standard deviation scores were negatively correlated with mean age (r: -0.354; P = .04) and height standard deviation scores (r: -0.353; P = .04). In the multivariate model, mean age and height standard deviation scores at renal transplant remained significantly associated with increases in height standard deviation scores (P = .018; ß coefficient: -0.341, 95% CI: -0.17; -0.002; and P = .005; ß coefficient: -0.431, 95% CI: -0.519; -0.101). CONCLUSIONS: Renal transplant improves linear growth by providing moderate or accelerated growth in prepubertal children.