Małgorzata Mizerska-Wasiak

Erratum to: Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy

Background nThe aim of this study was to evaluate the usefulness of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio for predicting histological severity of kidney lesions in children with IgA nephropathy (IgAN) based on World Health Organization (WHO) and the Oxford classification (OC).

Can We Further Improve the Quality of Nephro-Urological Care in Children with Myelomeningocele?

Myelomeningocele (MMC) results from a failure of normal neural tube fusion in early fetal development. Retrospective, observational study of medical data of 54 children treated in Pediatric Nephrology and Urology Clinics for five years was performed. The following data were analyzed: serum creatinine, eGFR, urine analysis, renal scintigraphy (RS), renal ultrasound, and urodynamics. Mean age of studied population: 12.3 years, median of eGFR at the beginning and at the end of survey was 110.25 and 116.5 mL/min/1.73 m2 accordingly. Median of frequency of urinary tract infections (fUTI): 1.2 episodes/year. In 24 children: low-pressure, in 30 children: high-pressure bladder was noted. Vesicouretral reflux (VUR) was noted in 23 children (42.6%). fUTI were more common in high-grade VUR group. High-grade VURs were more common in group of patients with severe renal damage. At the end of the survey 11.1% children were qualified to higher stages of chronic kidney disease. Renal parenchyma damage progression in RS was noted in 22.2% children. Positive VUR history, febrile recurrent UTIs, bladder wall trabeculation, and older age of the patients constitute risk factors of abnormal renal scans. More than 2.0 febrile, symptomatic UTIs annually increase by 5.6-fold the risk of severe renal parenchyma damage after five years.

Predictors of Progression in IgA Nephropathy in Childhood

The aim of this retrospective study was to assess the usefulness of potential predictors of poor prognosis in IgA nephropathy in children. The study population consisted of 55 children aged 11u2009±u20094xa0years, diagnosed on the basis of the Oxford classification and MEST score of kidney biopsy findings. Proteinuria, glomerular filtration rate (GFR), and the IgA/C3 serum ratio were assessed in all patients twice: at onset and at follow-up. The patients were treated with steroids, immunosuppressive drugs, and/or angiotensin-converting enzyme inhibitors. Follow-up was at 3.9u2009±u20092.9 (median 2.7) years. The patients were subdivided into two groups: with GFR <90 and ≥90xa0mL/min at follow-up. ROC AUC curves and logistic regression were used to evaluate the power of prognostic factors. The two groups did not differ regarding the level of proteinuria, MEST score, and the IgA/C3 ratio at onset of disease. There was a significant association between GFR reductions at onset and follow-up (AUCu2009=u20090.660; pu2009<u20090.05). In patients with nephrotic range proteinuria at onset, proteinuria at follow-up was more frequent compared with other patients (AUCu2009=u20090.760; pu2009<u20090.05), MEST score ≥3 tended to be associated with reduced GFR (AUCu2009=u20090.650; pu2009=u20090.07) but not with proteinuria (AUCu2009=u20090.608; pu2009=u20090.47), and the IgA/C3 ratio was higher (pu2009<u20090.05) at follow-up. No significant associations were found between the IgA/C3 ratio at onset and reduced GFR (AUCu2009=u20090.565; pu2009=u20090.46) or proteinuria at follow-up (AUCu2009=u20090.263; pu2009=u20090.20). We conclude that predictors of poor outcome in childhood IgAN include the following: GFR reduction, nephrotic range proteinuria at onset of disease, and high MEST score in Oxford classification of kidney biopsy. Despite a higher serum IgA/C3 ratio in children with impaired renal function in long-term follow-up, we failed to demonstrate a significant association between this ratio at onset of disease and reduced GFR or persistent proteinuria at follow-up. Thus, IgA/C3 ratio is not a good foreteller of progression of IgA nephropathy in childhood.

Treatment Outcomes in Children with Henoch-Schönlein Nephritis

The aim of the present study was to quantify the effects of treatment of children with Henoch-Schönlein nephritis (HSN) evaluated on the basis of kidney biopsy findings. Data were analyzed from 32 patients with HSN (mean age 9.3u2009±u20093.5xa0years, 19 with nephrotic syndrome/nephrotic proteinuria NS/NP, 13 with nephritic syndrome NphS), in whom the diagnosis was confirmed by kidney biopsy. Patients received immunosuppressive treatment (azathioprine or cyclophosphamide) and/or steroids and renoprotection according to a defined protocol. Patients were referred to a specific treatment protocol selected on the basis of clinical symptoms of nephropathy (NS/NP or NphS) and histopathological grade according to the WHO classification. Grade I-II changes were defined as mild HSN, and grade III-V WHO as severe HSN. The follow-up kidney biopsy was performed upon obtaining parental consent in 17 children. Following treatment, proteinuria resolved in 78u2009% children with mild HSN and 87u2009% children with severe HSN. In kidney biopsy, histological improvement was seen in 59u2009% children and no worsening in 35u2009%. We conclude that a flexible treatment protocol related to clinical symptoms and histological staging may contribute to a reduction of proteinuria and a delay in disease progression in children with HSN.

Candida spp. and gingivitis in children with nephrotic syndrome or type 1 diabetes

BackgroundDiabetes and Nephrotic syndrome (NS) promote plaque-related gingivitis and yeast-like fungal infections.The study assesses the impact of Candida spp. and general disease- or treatment-related factors on plaque-related gingivitis severity in children and adolescents with Nephrotic syndrome /diabetes.MethodsBody mass index (BMI), BMI standard deviation score, and oral cavity (Plaque Index – PLI,u2009Gingival Index – GI, mucosa status, presence and Candida enzymatic activity) were assessed in 96 patients (32 with NS: 30- immunosuppressive treatment, 35 - type 1 diabetes, and 29 generally healthy), aged; 3–18 years. Laboratory included cholesterol and triglyceride measurements; in diabetic subjects– glycated haemoglobin, in NS: total protein, albumin, creatinine, haemoglobin, haematocrit, white cell count, urinary protein excretion. Medical records supplied information on disease duration and treatment. A statistical analysis was performed; Kendall Tau coefficient, chi-square test, t-test, and multiple regression analysis ( Pu2009<u20090.05).ResultsCandida spp. often occurred in healthy patients, but oral candidiasis was found only in the NS and diabetes groups (9.37% and 11.43%). Gingivitis occurred more frequently in patients with NS/diabetes. Gingivitis severity was correlated with PLI, age, and yeast enzyme activity in NS – to with immunosuppressive treatment with >1 drug, drug doses, treatment duration, lipid disorders, and BMI; in diabetes, with blood glucose and glycated haemoglobin >8%.ConclusionPoor hygiene control is the main cause of gingivitis. Gingivitis severity is most likely related to age, lipid disorders and increase in body mass. Candida spp., in uncompensated diabetes and in those using immunosuppressive treatment, might intensify plaque-related gingivitis.

Prevalence of Hypertension in Children with Early-Stage ADPKD

BACKGROUND AND OBJECTIVESnAutosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnOur retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected.nnnRESULTSnData from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P=0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P=0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P=0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P=0.10).nnnCONCLUSIONSnThese data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages.

Dent disease in Poland: what we have learned so far?

PurposeDent disease (DD) is a rare tubulopathy characterized by proximal tubular dysfunction leading to chronic kidney disease (CKD). The aim of the study was to characterize patients with DD in Poland.MethodsA retrospective analysis of a national cohort with genetically confirmed diagnosis.ResultsOf 24 males, all patients except one carried mutations in the CLCN5 gene; in one patient a mutation in the OCRL gene was disclosed. Molecular diagnosis was delayed 1xa0year on average (range 0–21xa0years). The most common features were tubular proteinuria (100%), hypercalciuria (87%), and nephrocalcinosis (56%). CKD (≤stage II) and growth deficiency were found in 45 and 22% of patients, respectively. Over time, a progression of CKD and persistence of growth impairment was noted. Subnephrotic and nephrotic proteinuria (20%) was found in most patients, but tubular proteinuria was assessed in only 67% of patients. In one family steroid-resistant nephrotic syndrome prompted a genetic testing, and reverse phenotyping. Five children (20%) underwent kidney biopsy, and two of them were treated with immunosuppressants. Hydrochlorothiazide and angiotensin-converting enzyme inhibitors were prescribed for a significant proportion of patients (42 and 37.5%, respectively), while supplemental therapy with phosphate, potassium, vitamin D (12.5% each), and alkali (4.2%) was insufficient, when compared to the percentages of patients requiring repletion.ConclusionsWe found CLCN5 mutations in the vast majority of Polish patients with DD. Proteinuria was the most constant finding; however, tubular proteins were not assessed commonly, likely leading to delayed molecular diagnosis and misdiagnosis in some patients. More consideration should be given to optimize the therapy.

Renalase in Children with Glomerular Kidney Diseases

Studies suggest that renalase, a renal catecholamine-inactivating enzyme, plays a major role in the pathogenesis of kidney and cardiovascular diseases in adults. This study seeks to determine the role of renalase in children with glomerular kidney diseases. We evaluated the serum renalase, arterial stiffness, intima-media thickness, blood pressure, and clinical and biochemical parameters in 78 children (11.9xa0±xa04.6xa0years of age) with glomerulopathies such as idiopathic nephrotic syndrome (40 cases), IgA nephropathy (12 cases), Henoch-Schönlein nephropathy (12 cases), and other glomerulopathies (14 cases). The control group consisted of 38 healthy children aged 11.8xa0±xa03.3 years. The mean renalase was 25.74xa0±xa08.94xa0μg/mL in the glomerulopathy group, which was not significantly different from the 27.22xa0±xa05.15 in the control group. The renalase level did not differ among various glomerulopathies either. However, proteinuric patients had a higher renalase level than those without proteinuria (28.43xa0±xa011.71 vs. 24.05xa0±xa06.23, respectively; pxa0=xa00.03). In proteinuric patients, renalase correlated with daily proteinuria. In the entire glomerulopathy group, renalase correlated with age, systolic central blood pressure (BP), diastolic peripheral and central BP, mean peripheral and central BP; peripheral diastolic BP Z-score, glomerular filtration rate, cholesterol, triglycerides, and pulse wave velocity. We conclude that in children with glomerulopathies renalase, although basically not enhanced, may underlie blood pressure elevation and arterial damage.

Enzymatic Activity of Candida spp. from Oral Cavity and Urine in Children with Nephrotic Syndrome

Oral colonization with Candida spp. is not synonymous with a systemic active infection. The aim of the study was to evaluate enzymatic activity of Candida strains isolated from the oral cavity in patients with nephrotic syndrome (NS) and to compare it with the activity determined in urine. We studied 32 children with NS and 26 control healthy children. Children with NS were treated with glucocorticosteroids, cyclosporin A, mycophenolate mofetil or azathioprine. In all children, API-ZYM enzymatic tests were performed to evaluate hydrolytic enzymes of Candida isolated from the oral cavity and in urine. Candida spp. were isolated from the oral cavity in 11 patients with NS (34.4%), all receiving immunosuppressive treatment. All strains produced valine arylamidase, 9 alpha-glucosidase (E16), and 9 N-acetyl-beta-glucosaminidase (E18). A positive correlation between the presence of Candida in the oral cavity and E16 and E18 enzymatic activity in both oral cavity and urine was found. A dose of cyclosporin A had an effect on the enzymatic activity (p < 0.05). We conclude that immunosuppressive treatment of NS in children may predispose to systemic Candida invasion. The results of this study suggest that oral candida infection should be monitored in children with nephrotic syndrome, particularly those treated with immunosuppressive agents.

IgA Nephropathy in Children: A Multicenter Study in Poland.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis in pediatric population. The clinical presentation of the disease in children ranges from microscopic hematuria to end-stage kidney disease. The aim of the study was to retrospectively assess clinical and kidney biopsy features in children with IgAN. We assessed a cohort of 140 children, 88 boys, 52 girls with the diagnosis of IgAN in the period of 2000-2015, entered into the national Polish pediatric IgAN registry. The assessment included the following: proteinuria, hematuria, glomerular filtration rate (GFR), arterial blood pressure, and the renal pathological changes according to the Oxford classification and crescents formation, as modifiable and unmodifiable risk factors. The incidence of IgAN in Poland was set at 9.3 new cases per year. The mean age at onset of IgAN was 11.9u2009±u20094.3xa0years, and the most common presentation of the disease was the nephritic syndrome, recognized in 52u2009% of patients. Kidney biopsy was performed, on average, 1.3u2009±u20092.0xa0years after onset of disease. Based on the ROC analysis, a cut-off age at onset of disease for GFR <90xa0mL/min/1.73xa0m2 (risk factor of progression) was calculated as 13.9xa0years. Unmodifiable lesions: segmental sclerosis, tubular atrophy/interstitial fibrosis (S1, T1-2) in the Oxford classification and crescents in kidney biopsy were significantly more common in Gr 1 (>13.9xa0years) compared with Gr 2 (<13.9xa0years), despite a significantly shorter time to kidney biopsy in the former. We conclude that IgAN in children may be an insidious disease. A regular urine analysis, especially after respiratory tract infections, seems the best way for an early detection of the disease.