Min Hwa Son

Prolonged exposure to fine particulate matter (PM_2.5) has been implicated in accelerated aging, including organ fibrosis. This study aimed to investigate whether prenatal and postnatal PM_2.5 exposure promotes renal fibrogenesis in adulthood and whether long-term vitamin D supplementation alleviates associated renal injury. Pregnant Sprague-Dawley rats were randomly assigned to three groups: control (normal saline, NS), PM_2.5 exposure, and PM_2.5 exposure with vitamin D supplementation during gestation and lactation (n = 3/group). Male offspring were subsequently exposed to the same conditions from postnatal weeks 3 to 8 (n = 7/group). On postnatal day 56, PM_2.5-exposed rats showed lower body weight and more severe glomerular and tubulointerstitial damage compared to controls. Serum calcium levels were elevated in the PM_2.5 group. The expression of intrarenal renin, transforming growth factor-β1, α-smooth muscle actin, and vimentin was upregulated, accompanied by increased collagen deposition. Long-term vitamin D supplementation reversed most of these changes, except for intrarenal vimentin expression and serum calcium levels. These findings indicate that prenatal and postnatal PM_2.5 exposure can activate intrarenal renin signaling and fibrogenic pathways, contributing to renal fibrosis later in life. Long-term vitamin D supplementation may provide partial protective effects against PM_2.5-induced renal fibrogenesis.

Background: Nutcracker syndrome (NCS) has been reported to coexist with various glomerulonephritis (GN). This study investigated clinical features of NCS combined with GN in a pediatric case series and the possible relationship between these two conditions.Methods: Clinical and pathologic findings of 15 children with NCS and biopsy-proven GN were analyzed. NCS was diagnosed with renal Doppler ultrasonography, abdominal computed tomography, and/or magnetic resonance imaging. Glomerular lesions were divided into two pathological categories: minor glomerular abnormalities (MGAs) and definite GN. Results: Mean age of all patients was 11 ± 3.36 years and mean follow-up duration was 53.8 ± 29.3 months. Chief complaint was proteinuria with or without hematuria. During follow-up, five patients developed left kidney enlargement. Abnormal levels in immunological tests were revealed in 10 patients. Extrarenal symptoms including gonadal varicocele, splenic cyst, syncope, and anemia were found in seven patients. On kidney biopsy, seven patients had MGAs and eight children showed definite GN (one case of focal GN, one case of mesangial proliferative GN, one case of focal segmental glomerulosclerosis, two cases of immunoglobulin A [IgA] vasculitis nephritis, and three cases of IgA nephropathy). While the MGA group showed a higher proportion of isolated proteinuria and a lower estimated glomerular filtration rate (eGFR) at the last visit, there were no differences in age, clinical features of NCS, extrarenal symptoms, immunological tests, and eGFR decline rate between the two groups.Conclusion: NCS may be associated with the presence of various GN. The causal relationship between NCS and GN should be further investigated.

Background: Little is known about the transgenerational effects of maternal exposure to fine particulate matter (PM2.5) on offspring kidney health. This study investigated the effect of maternal administration of PM2.5 or PM2.5 with vitamin D during pregnancy and lactation on renal injury in rat dams and their offspring. Methods: Nine pregnant Sprague-Dawley rats received oral administration of normal saline, airborne PM2.5, or PM2.5 with vitamin D from gestational day 11 to postpartum day 21. Kidneys of rat dams (n = 3 for each group) and their male offspring (n = 5 for each group) were taken for analysis on postpartum or postnatal day 21. Results: Maternal PM2.5 exposure increased glomerular damage, tubulointerstitial injury, and cortical macrophage infiltration in both dams and pups; all increases were attenuated by vitamin D administration. In dam kidneys, PM2.5 increased the protein expression of vitamin D receptor (VDR), klotho, and tumor necrosis factor-α; vitamin D lessened these changes. The expressions of renin, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappa B (NF-κB) p50 decreased in rat dams exposed to PM2.5. In offspring kidneys, exposure to maternal PM2.5 reduced the expression of VDR, renin, angiotensin-converting enzyme (ACE), Nrf2, and NF-κB p50, but increased cytochrome P450 24A1 expression. Maternal vitamin D administration with PM2.5 enhanced VDR, ACE, and NF-κB p50 activities in pup kidneys. Conclusion: PM2.5 exposure during nephrogenesis may exert transgenerational renal impairment, and maternal vitamin D intake could attenuate PM2.5-induced kidney damage in mothers and their offspring.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare entity characterized by the presence of lupus anticoagulant (LA) and prothrombin (factor II) deficiency. It may cause severe bleeding contrary to classical antiphospholipid syndrome. Here, we report a case of LAHPS presenting with a hemorrhagic ovarian cyst in a 17-year-old girl with systemic lupus erythematosus (SLE) nephritis. She had been followed up for 8 years. Her first manifestation of SLE was prolonged gingival bleeding after tooth extraction at 9 years of age. During the follow-up period, she had neither severe bleeding nor thrombotic complications despite a positive LA and a prolonged activated partial thromboplastin time (aPTT). At this visit, the patient presented with colicky abdominal pain, a hemorrhagic ovarian cyst, a prolonged prothrombin time, a prolonged aPTT, a low factor II level, and a positive LA, leading to the diagnosis of LAHPS. While a hemorrhagic ovarian cyst resolved completely in 3 months, she received oral pill, transfusions of red blood cells and plasma, and intravenous cyclophosphamide pulse therapy in combination with glucocorticoids due to persistent menorrhagia, anemia, prolonged aPTT, and lupus flaring. Thus, LAHPS needs to be considered in SLE patients with positive LA and prolonged aPTT.

Background Nutcracker syndrome (NCS) has been reported to coexist with various glomerulonephritis (GN). This study investigated clinical features of NCS combined with GN in a pediatric case series and the possible relationship between these two conditions. Methods Clinical and pathologic findings of 15 children with NCS and biopsy-proven GN were analyzed. NCS was diagnosed with renal Doppler ultrasonography, abdominal computed tomography, and/or magnetic resonance imaging. Glomerular lesions were divided into two pathological categories: minor glomerular abnormalities (MGAs) and definite GN. Results Mean age of all patients was 11 ± 3.36 years and mean follow-up duration was 53.2 ± 28.7 months. Chief complaint was proteinuria with or without hematuria. During follow-up, five patients developed left kidney enlargement. Abnormal levels in immunological tests were revealed in 10 patients. Extrarenal symptoms including gonadal varicocle, splenic cyst, syncope, and anemia were found in 7 patients. On kidney biopsy, 7 patients had MGAs and 8 children showed definite GN (one case of focal GN, one case of mesangial proliferative GN, one case of focal segmental glomerulosclerosis, two cases of IgA vasculitis nephritis, and three cases of IgA nephropathy). While there were no differences in age, baseline estimated glomerular filtration rate (eGFR), immunological tests, clinical features of NCS, or extrarenal symptoms between the two groups, patients with NCS combined with MGAs showed higher proportion of isolated proteinuria and eGFR decline (both P < 0.05). Conclusions NCS may be associated with the presence of various GN. The causal relationship between NCS and GN should be further investigated.

Purpose: Recurrent urinary tract infections (UTIs) in children is a major challenge for pediatricians. This study was designed to investigate the risk factors for recurrent UTIs and determine the association between recurrent UTIs and clinical findings, including growth patterns in infants and children younger than 24 months of age. Methods: We retrospectively reviewed the medical records of 147 patients <24 months of age with UTIs who were hospitalized between August 2018 and October 2021. The patients were divided into recurrent and single UTI episode groups. Clinical findings and anthropometric and laboratory data were compared between the two groups.Results:In the recurrent UTI group, the weight-for-length (WFL) percentile at the first UTI diagnosis was lower compared to the single UTI episode group, and the weight-for-age percentile at 3-month and 6-month follow-ups after the first UTI decreased (all P<0.05). In univariable logistic regression analysis, higher birth weight, lower WFL percentile, the presence of hydronephrosis, acute pyelonephritis or vesicoureteral reflux, the use of prophylactic antibiotics, and non-Escherichia coli infections were associated with the development of recurrent UTIs (all P<0.05). However, in the multivariable analysis, only the presence of hydronephrosis and prophylactic antibiotic use were independently related to UTI recurrence (P<0.05). Conclusion: The presence of hydronephrosis at the first UTI can be helpful for predicting UTI recurrence in young children aged < 24 months. Antibiotic prophylaxis may be associated with UTI recurrence. Potential growth delay should be carefully monitored in infants with recurrent UTI.

Cystinuria, a genetically inherited disorder, is a rare cause of kidney stones. It is characterized by impaired transport of cystine and amino acids in the proximal renal tubule and the small intestine. Most patients develop cystine stones throughout their lifetime. Recurrent renal stones need to be extracted by repeated urologic interventions. Treatment options of cystinuria for preventing stone recurrence are limited and poorly tolerated. In this study, we report a pediatric case of cystinuria with a heterozygous SLC3A1 mutation diagnosed by stone analysis, measurement of urine cystine excretion, and genetic analysis. There were recurrent renal stones despite repetitive shock wave lithotripsy and retrograde intrarenal surgery. However, the rate of stone formation seemed to be slower after D-penicillamine was added into adequate hydration and urinary alkalinization.

Nutcracker syndrome (NCS) is a disease caused by compression of the left renal vein between the superior mesenteric artery and the abdominal aorta. Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by the predominance of IgA deposits in the glomerular mesangial area. Hematuria and proteinuria can be present in both diseases, and some patients can be concurrently diagnosed with NCS and IgAN; however, a causal relationship between the two diseases has not yet been clarified. Here, we report two pediatric cases of NCS combined with IgAN. The first patient presenting with microscopic hematuria and proteinuria was diagnosed with NCS at the initial visit, and the second patient was later diagnosed with NCS when proteinuria worsened. Both patients were diagnosed with IgAN based on kidney biopsy findings and treated with angiotensin-converting enzyme inhibitors and immunosuppressants. A high index of suspicion and timely imaging or biopsy are essential for the proper management of NCS combined with glomerulopathy.

Background To determine whether urine neutrophil gelatinase-associated lipocalin (uNGAL) might be superior to pyuria for detecting urinary tract infection (UTI) regardless of urine specific gravity (SG) in young children. Methods We conducted a retrospective analysis of children aged < 3 years who were evaluated for UTI with urinalysis, urine culture, and uNGAL measurements during a 5-year period. Sensitivity, specificity, likelihood ratios (LRs), predictive values (PVs), area under the curves (AUCs) of uNGAL cut-off levels, and various microscopic pyuria thresholds for detecting UTI were calculated for dilute (SG < 1.015) and concentrated urine (SG ≥ 1.015). Results Of 456 children included, 218 had UTI. The diagnostic value of urine white blood cell (WBC) concentration to define UTI changed with urine SG. For detecting UTI, uNGAL cut-off of 68.4 ng/mL had higher AUC values than pyuria ≥ 5 WBCs/high power field (HPF) for dilute and concentrated urine samples (both P < 0.05). Positive LR and PV and specificity of uNGAL were all greater than those of pyuria ≥ 5 WBCs/HPF regardless of urine SG, although the sensitivity of pyuria ≥ 5 WBCs/HPF was higher than that of uNGAL cut-off for dilute urine (93.8% vs. 83.5%) (P < 0.05). At uNGAL ≥ 68.4 ng/mL and ≥ 5 WBCs/HPF, posttest probabilities of UTI were 68.8% and 57.5% for dilute urine and 73.4% and 57.3% for concentrated urine, respectively. Conclusions Urine SG can affect the diagnostic performance of pyuria for detecting UTI and uNGAL might be helpful for identifying UTI regardless of urine SG in young children. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

The messenger RNA-based vaccine for the coronavirus disease 2019 (COVID-19) may induce glomerulonephritis, including immunoglobulin A nephropathy (IgAN). New-onset IgAN triggered by vaccination against COVID-19 has been reported rarely, especially in children. Herein, we report a pediatric case of newly diagnosed IgAN after administration of the Pfizer vaccine for COVID-19. A 12-year-old girl was referred to our hospital for evaluation of gross hematuria after inoculation with the second dose of Pfizer’s COVID-19 vaccine; she had no adverse effects after the first dose. At the time of admission, she showed heavy proteinuria and persistent hematuria. Kidney biopsy revealed an IgAN, and she was treated with an oral steroid and an angiotensin-converting enzyme inhibitor. Four months after discharge, the proteinuria and hematuria resolved completely.