Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the ...course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.
Background
C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data ...regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G.
Methods
Sixty pediatric patients with C3G from 21 referral centers in Turkey were included in this retrospective study. Patients were categorized according to CKD stage at last visit as CKD5 or non-CKD5. Demographic data, clinicopathologic findings, treatment, and outcome data were compared and possible risk factors for CKD5 progression determined using Cox proportional hazards model.
Results
Mean age at diagnosis was 10.6 ± 3.0 years and follow-up time 48.3 ± 36.3 months. Almost half the patients had gross hematuria and hypertension at diagnosis. Nephritic-nephrotic syndrome was the commonest presenting feature (41.6%) and 1/5 of patients presented with nephrotic syndrome. Membranoproliferative glomerulonephritis was the leading injury pattern, while 40 patients had only C3 staining. Patients with DDD had significantly lower baseline serum albumin compared with C3GN. Eighteen patients received eculizumab. Clinical remission was achieved in 68.3%. At last follow-up, 10 patients (16.6%) developed CKD5: they had lower baseline eGFR and albumin and higher frequency of nephrotic syndrome and dialysis requirement than non-CKD5 patients. Lower serum albumin and eGFR at diagnosis were independent predictors for CKD5 development.
Conclusions
Children with C3G who have impaired kidney function and hypoalbuminemia at diagnosis should be carefully monitored for risk of progression to CKD5.
Graphical abstract
The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth ...hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort.
Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group.
Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score.
Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The Turkish Renal Tubular Disorders Working Group aimed to form a patient registry database and gathered demographic, clinical, and laboratory data in various hereditary renal tubular ...disorders (HRTDs).
Methods
A questionnaire comprising HRTDs was sent to the centers. The cohort was composed of 226 patients (109 girls, 117 boys).
Results
The distribution of patients according to HRTD was as follows: 45.6% distal renal tubular acidosis (dRTA), 26.6% proximal RTA (pRTA), 3.5% type IV RTA, 21.7% Bartter’s syndrome, and 2.6% Gitelman’s syndrome. Cystinosis was the most common cause for renal Fanconi syndrome. Age at diagnosis was between 1 month and 16 years. Overall consanguinity rate was as high as 72%. Rate of affected siblings was 28.5%. pRTA and type IV RTA were more common in males. Most common presenting symptoms were failure to thrive, lack of appetite, and vomiting. Nephropathic cystinosis was the most common HRTD leading to renal failure, followed by dRTA. Hearing loss was present in 23% of patients with dRTA and 6.3% of patients with Bartter’s syndrome. No other patient had hearing loss. Convulsions were noted in Bartter’s syndrome patients with failure to thrive, especially in those with height below 3%. Polyuria and nephrocalcinosis were more common in dRTA patients with deafness compared with patients without deafness.
Conclusions
This data reflected a high number of HRTDs as a result of high consanguinity rate in Turkey. Our data serve as a database of demographic, clinical, and laboratory features of this rare disease group.
Background
C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The ...aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes.
Methods
Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan–Meier analysis was performed for kidney survival.
Results
Out of the 60 patients, 17 had mutations. The most common mutation was in the
CFH
gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years,
p
= 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%,
p
= 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group.
Conclusions
This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
•The prevalence of NPSLE is 13.5% in pediatric SLE patients in Turkey.•Clinical and laboratory features of SLE and NP involvement are grouped in five clusters.•APA positivity, high SLEDAI scores and ...plasmapheresis are risk factors for neurological sequelae.
Neuropsychiatric (NP) involvement is a restricted area in juvenile-onset systemic lupus erythematosus (jSLE).
To investigate the prevalence, demographic and clinical features, and outcomes of the neurological involvement in the Turkish jSLE population.
This study was based upon 24 referral centers’ SLE cohorts, multicenter and multidisciplinary network in Turkey. Patient data were collected by a case report form which was standardized for NP definitions according to American Collage of Rheumatology (ACR). Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) neuropsychiatric part was used to determine NP damage. Variables were evaluated Ward's hierarchical clustering analyses, univariate, and multivariate logistic regression analyses.
A hundred forty-nine of 1107 jSLE patients had NP involvement (13.5%). The most common NPSLE findings were headache (50.3%), seizure (38.3%), and acute confusional state (33.6%). Five clusters were identified with all clinical and laboratory findings. The first two clusters involved neuropathies, demyelinating diseases, aseptic meningitis, and movement disorder. Cluster 3 involved headache, activity markers and other SLE involvements. Idiopathic intracranial hypertension, cerebrovascular disease, cognitive dysfunction, psychiatric disorders and SLE antibodies were in the fourth, and acute confusional state was in the fifth cluster. In multivariate analysis, APA positivity; OR: 2.820, (%95CI: 1.002–7.939), P: 0,050, plasmapheresis; OR: 13.804 (%95CI: 2.785–68.432), P: 0,001, SLEDAI scores; OR: 1.115 (%95CI: (1.049–1.186), P: 0,001 were associated with increased risk for neurologic sequelae.
We detected the prevalence of juvenile NPSLE manifestations in Turkey. We have identified five clusters that may shed light pathogenesis, treatment and prognosis of NP involvements. We also determined risk factors of neurological sequelae. Our study showed that new definitions NP involvements and sequelae for childhood period are needed.
OBJECTIVETo investigate the effect of the time period under the rubble on morbidity and mortality of the crush-syndrome patients after the catastrophic Marmara earthquake that struck northwestern ...Turkey in August 1999.
DESIGNObservational study.
SETTINGConsecutive admissions to emergency and intensive care units of 35 reference hospitals that treated the renal victims.
METHODSAnalysis of questionnaires obtained from these hospitals.
PATIENTSA total of 539 of 639 crush-syndrome patients whose time under the rubble was identified in the questionnaires.
RESULTSMean time under the rubble was 11.7 ± 14.3 hrs (median, 8 hrs; interquartile range, 6 hrs; range, 0.5–135 hrs). The highest number of patients was entrapped within the 5–8 hrs time stratum, and by the end of 48 hrs, 97% of the victims had been rescued. Nondialyzed victims spent a longer duration under the rubble than dialyzed ones (15.9 ± 23.1 hrs median, 7 hrs; interquartile range, 8.5 hrs vs. 10.3 ± 9.5 hrs median, 8 hrs; interquartile range, 6 hrs), p < .001). Likewise, in the strata of longer time under the rubble, the percentage of survivors was higher (p = .07). Time under the rubble correlated positively with the number of amputated extremities (p < .001) and admission platelet count (p < .001), and it correlated negatively with admission serum albumin (p < .001). The victims entrapped for >50 hrs (n = 6) were characterized by lower figures of admission blood urea nitrogen (p = .04), serum creatinine (p = .003), hemodialysis sessions, and duration of hemodialysis support (p = .005, for both analyses) compared with victims whose time under the rubble was shorter.
CONCLUSIONRescue efforts should continue at least for 5 days after the disaster. Time under the rubble is not an adverse prognostic indicator of survival or renal dysfunction for the patients of crush syndrome, probably because only the victims with mild or moderate injuries can survive under the rubble for longer durations.
Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict ...CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6–17 years with baseline estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69–0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.
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