Visit-to-visit blood pressure variability in children and adolescents with renal disease

Background

Increase in blood pressure (BP) variability (BPV) is associated with cardiovascular events, target organ damage, and arterial stiffness in adults. We previously reported that 24-h BPV may be associated with arterial stiffness and underlie white-coat hypertension (WCH). In this study, we examined whether visit-to-visit variability (VVV) could predict WCH and whether VVV correlated with eGFR, eGFR slope, and albuminuria/proteinuria in children and adolescents with renal diseases.

Methods

VVV was determined as average real variability of office BP measurements between visits, and 24-h BPV as the standard deviation of 24-h ambulatory BP. In 35 renal patients (25 boys and 10 girls, 7–18 years of age), divided into normotension (NT), WCH, and hypertension (HTN), the relationships between VVV and 24-h BPV and VVV in each BP category were studied. In separate 48 renal patients (24 boys and 24 girls, 2–18 years of age), the correlation between VVV and eGFR, eGFR slope, urine albumin or protein excretion was examined.

Results

Systolic VVV was significantly correlated with systolic office BP index. There was no correlation between VVV and 24-h BPV or 24-h pulse pressure. In addition, VVV was not different among NT, WCH, and HTN. Systolic VVV was significantly negatively correlated with eGFR but not with eGFR slope, albuminuria, or proteinuria. A cut-off value of systolic VVV for detecting eGFR?<?60 ml/min per 1.73 m² was 8.5.

Conclusion

VVV could not predict WCH. Systolic VVV correlated with eGFR but not with eGFR slope, albuminuria/proteinuria. Increased VVV could be a marker of decreased eGFR.

     

Effect of placebo on ambulatory blood pressure monitoring in children

Background

Ambulatory blood pressure monitoring (ABPM) has been proposed as a useful tool for more accurately diagnosing hypertension (HTN) and evaluating blood pressure (BP) response in pediatric anti-hypertensive trials. ABPM captures multiple BP measurements during routine daily activities and is thus an excellent method for identifying white-coat HTN. Additionally, ABPM measurements in adults do not demonstrate the placebo effect commonly seen with casual BP measurements, although this has yet to be evaluated in children. Therefore,, the aim of this study was to assess the effect of placebo on ABPM measurements in children.

Methods

A total of 141 children aged 5–16 years with elevated BP were randomized into a multi-center, single-blind, cross-over trial. Subjects received a placebo pill prior to wearing a 24-h ABPM device at one of two visits separated by 1–2 weeks. Study procedures were otherwise identical at both visits.

Results

Mean systolic and diastolic BP for all measured time periods were similar between visits, as was the number of children diagnosed with HTN at each visit.

Conclusion

Having confirmed HTN at baseline did not affect the impact of placebo on mean BP. If confirmed, this lack of placebo effect on ABPM measurements may allow for the design of direct comparison pediatric anti-hypertensive trials without a placebo arm.     

Increased urinary angiotensinogen is an effective marker of chronic renal impairment in very low birth weight children

Background

Recent advancements in perinatal and neonatal care have increased the survival of preterm infants with lower birth weight and very low birth weight (VLBW; < 1,500 g) infants. Such infants are exposed to a higher risk of renal insufficiency in later life due to congenitally fewer nephrons; however, urinalysis in order to detect renal insufficiency in those infants at school age has not yet been established. The aim of the study was to assess chronic renal impairment in VLBW infants during their childhood after discharge from the neonatal intensive care unit (NICU) until adolescence using urinary angiotensinogen (uAGT).

Methods

We compared serum levels of angiotensinogen (sAGT), creatinine, β₂-microglobulin (sβ2MG) and cystatin C (sCysC), and urinary levels of uAGT, creatinine (uCre),β₂-microglobulin (uβ2MG) and albumin between two infant groups—the VLBW group (50 children who were admitted to our NICU as infants), and a control group of 25 children who were born as full-term infants with birth weight ≥2,500 g. The median age of the VLBW group and control group infants was 60 months (range 7–135) and 57 months (range 5–144), respectively, at the time of evaluation.

Results

In the VLBW group, sCysC levels were high (p < 0.05) and estimated glomerular filtration rate (eGFR) was low (p < 0.05). There were no significant differences in the ratios of uβ2MG to creatinine and urinary albumin to creatinine between the two groups. Although there were no differences in concentration of sAGT between the two groups (p = 0.062), the ratio of uAGT to creatinine was significantly higher in the VLBW group (p < 0.01). The examination of 19 VLBW infants (19/50) with eGFR ≤90 ml/min/1.73 m² showed a positive correlation between uAGT/creatinine and urinary albumin/creatinine (r = 0.531, p?VLBW infants (19/50) with eGFR ≤90 ml/min/1.73 m², 18 of whom had stage II chronic kidney disease and one who had stage III disease (r = ?0.512, p ≤ 0.05).

Conclusions

uAGT is an effective marker for predicting the progression of chronic renal impairment in preterm VLBW infants after their growth. uAGT measurement is easier to conduct, less invasive and more sensitive than conventional uβ2MG or urinary albumin measurement.     

Ambulatory blood pressure in prehypertensive children and adolescents

Background

Prehypertension is defined as blood pressure (BP) ≥90th percentile, or ≥120/80?mmHg, but <95th percentile for age, sex, and height. Since the definition is made by conventional BP measurements and office BP can be quite variable, we studied whether prehypertension could be differentiated by ambulatory BP monitoring from normotension or hypertension (HTN) in children and adolescents.

Methods

One hundred and fifty-eight children (84 boys and 74 girls, aged 6–17?years, median 12) were studied. According to the office BP values, they were divided into normotension (80), prehypertension (20), and HTN (58).

Results

Systolic BP index and systolic daytime ambulatory BP (ABP) were significantly higher in prehypertensive patients than in normotensives and lower than hypertensives. When daytime ABP was used to diagnose HTN, four normotensive (5.0%), four prehypertensive (20.0%), and 27 hypertensive (46.6%) patients had HTN. Thus, in patients with prehypertension, the prevalence of masked HTN is significantly higher than in those with normotension. On the other hand, the prevalence of daytime ambulatory HTN is significantly lower, i.e., white-coat effect is more frequent, compared with hypertensive patients.

Conclusion

Prehypertension lies between normotension and HTN in ABP values as well and is a good candidate for identifying masked HTN. Our data emphasize the importance of identifying prehypertension in children and adolescents.     

Cystatin C-based equation for estimating glomerular filtration rate in Japanese children and adolescents

Background

Renal inulin clearance is the gold standard for evaluation of kidney function, but is compromised by problems of collecting urine samples in children, especially those <6 years or with a bladder dysfunction. Therefore, we should utilize the serum cystatin C (cysC)-based estimated glomerular filtration rate (eGFR) for measuring serum cysC. The purpose of the present study is to determine the applicability of the new serum cysC-based eGFR in Japanese children and adolescents, including infants with chronic kidney disease (CKD), for evaluation of renal function.

Methods

Inulin clearance and standardized serum cysC level determined by the colloidal gold immunoassay were measured in 135 pediatric CKD patients between the ages of 1 month and 18 years with no underlying disease that affects renal function except CKD, to determine serum cysC-based eGFR in Japanese children and adolescents.

Results

We showed the inulin clearance by expression of 1/serum cysC in pediatric CKD patients, which resulted in the equation: inulin GFR (mL/min/1.73 m²) = 104.1 × 1/serum cysC (mg/L) ? 7.80. We also validated the cysC-based eGFR formula for Japanese adults. eGFR values obtained with the adult formula significantly underestimated GFR by approximately 8 % in children with CKD.

Conclusion

We determined the new cysC-based eGFR formula is useful for clinical screening of renal function in Japanese children and adolescents, including infants.     

Albuminuria is an independent predictor of all-cause and cardiovascular mortality in the Japanese population: the Takahata study

Background

Albuminuria is a known risk factor for cardiovascular events and premature deaths. However, the association between urinary albumin excretion and mortality is unknown in the Japanese population. To clarify this, we conducted a community-based longitudinal study.

Methods

This study included 3,445 registered Japanese subjects (mean age 62.6 years), with a 7-year follow-up. Albuminuria was defined as a urine albumin-creatinine ratio (ACR) ≥30 mg/g in the morning spot urine.

Results

Subjects with albuminuria (n = 514, 14.9 %) were older and showed a higher prevalence of hypertension, obesity, and diabetes and lower values of estimated glomerular filtration rate (eGFR) than those without albuminuria (n = 2931, 85.1 %). During the follow-up, 138 subjects died. A Kaplan–Meier analysis showed that all-cause mortality significantly increased along with the increase in urine albumin excretion (log-rank test, P < 0.001). The subjects with albuminuria showed a significantly higher mortality rate than those without albuminuria (7.4 vs. 3.4 %; log-rank test, P < 0.001). A Cox proportional hazard model analysis after adjusting for possible confounders showed that albuminuria was an independent risk factor for all-cause and cardiovascular mortality (hazard ratio [HR] 1.69, 95 % confidence interval [CI] 1.12–2.56 and HR 2.27, 95 % CI 1.10–4.70, respectively) but not for noncardiovascular mortality. These associations were preserved after excluding subjects with high ACR (≥300 mg/g).

Conclusions

Albuminuria was a risk factor for all-cause and cardiovascular mortality in the Japanese population. To detect subjects with a high risk for premature death, measuring urinary albumin excretion might be useful.     

Weight loss independently predicts urinary albumin excretion normalization in morbidly obese type 2 diabetic patients undergoing bariatric surgery

Background

Despite obesity being closely associated with two common risk factors for albuminuria, namely type 2 diabetes mellitus (T2DM) and hypertension, information on the impact of weight loss on albumin excretion rate in morbidly obese (MO) subjects is scarce.

Objective

To evaluate the independent contribution of weight loss following bariatric surgery (BS) to the improvement of the albumin-to-creatinine ratio (ACR) in MO subjects with T2DM.

Subjects and methods

Observational prospective study, including consecutive (n = 255) patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) of whom 37.6 % (n = 96) presented with T2DM. Stepwise logistic regression analysis was used to assess the contribution of T2DM-related, hypertension-related, and weight loss-related variables, and type of surgery to normalization of ACR (<30 mg/g) at 12 and 24 months follow-up.

Results

In T2DM subjects, baseline ACR was 85.7 ± 171 mg/g with ACR ≥30 mg/g being present in 45.7 % of the cohort. At 12 months, the ACR significantly decreased in T2DM subjects (42.2 ± 142.8 mg/g; p < 0.005) with no further reduction at 24 months after surgery (44.4 ± 227.7; p = 0.862). Among T2DM subjects with ACR ≥30 mg/g at baseline, the ACR became <30 mg/g in 58.5 % and 76.9 % at 12 and 24 months, respectively (p < 0.001 relative to baseline). Body mass index (BMI) change from baseline was the only independent predictor of ACR normalization at 12 months [Exp(B) 1.373, 95 % confidence interval 1.075–1.703; p < 0.05]. None of the evaluated variables appeared as an independent predictor of ACR normalization at 24 months.

Conclusions

Our data suggest that, in MO subjects with T2DM, interventions aiming at slowing the progression of nephropathy should not only focus on optimization of glucose and blood pressure control but also include effective weight loss strategies.     

Prevalence of Undiagnosed and Inadequately Treated Type 2 Diabetes Mellitus,Hypertension, and Dyslipidemia in Morbidly Obese Patients Who Present for Bariatric Surgery

Background

Pharmacotherapy is considered the primary treatment modality for diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DYS). We sought to investigate the status of DM, HTN, and DYS in patients who seek bariatric surgery.

Methods

Demographic and comorbidity history were prospectively collected on 1,508 patients referred for bariatric consultation at a single institution from February 2008 to March 2012. We utilized published consensus guidelines (GL) to benchmark the efficacy of standard pharmacotherapy for these metabolic diseases, and 881 patients met the study design criteria.

Results

Most patients exhibited at least one form of metabolic dysregulation (pre-DM or DM, 75.8 %; pre-HTN or HTN, 91.1 %; pre-DYS or DYS, 84.0 %; metabolic syndrome, 76.0 %). The majority of patients either did not meet GL treatment goals (DM, 45.7 %; HTN, 39.5 %; DYS, 22.3 %) or were previously undiagnosed (DM, 15.8 %; HTN, 13.7 %; DYS, 41.7 %). Non-GL pharmacotherapy was significantly less effective than GL pharmacotherapy at achieving treatment goals for DM (31.8 vs 53.2 %, p?<?0.001) and HTN (43.6 vs 63.2 %, p?=?0.007). Patients with concurrent DM, HTN, and DYS (35.5 %) were less likely than patients with only one or two of these metabolic diseases to achieve GL treatment goals for HTN (38.1 vs 72.6 %, p?<?0.001) and DYS (55.7 vs 73.8 %, p?=?0.002). Only 8.0 % of these patients achieved treatment goals for all three metabolic comorbidities.

Conclusions

In this patient group, DM, HTN, and DYS were poorly compensated, even when pharmacotherapy was consistent with published GL. This may be due to disease burden in bariatric surgery candidates or to inadequate medical management prior to presentation.     

Should mean arterial pressure be included in the definition of ambulatory hypertension in children?

Background

The diagnosis of hypertension (HTN)/normotension (NT) on ambulatory blood pressure monitoring (ABPM) is usually based on systolic (SBP) or diastolic blood pressure (DBP). The goal of this study was to analyze whether inclusion of mean arterial pressure (MAP) improves the detection of HTN on ABPM.

Methods

We retrospectively studied ABPM records in 229 children (116 boys, median age?=?15.3 years) who were referred for evaluation of HTN. A diagnosis of HTN was made if: (A) MAP or SBP or DBP was ≥1.65 SDS (95th percentile); (B) SBP or DBP was ≥1.65 SDS (95th percentile), during 24-h or daytime or night-time in both definitions.

Results

Using definition A, 46/229 patients had HTN compared to definition B by which only 37/229 patients had HTN (p?=?0.001). The level of agreement between the two definitions was very good (kappa?=?0.86?±?0.04), however nine patients (19.5 %) were missed by not using MAP in the definition of HTN. These nine patients had only mild HTN with a median Z score of 1.69.

Conclusions

The inclusion of MAP in the definition of ambulatory HTN significantly increased the number of hypertensive patients. MAP may be very helpful in detecting mild HTN in patients with normal/borderline SBP and DBP.     

More radial shortening after low-energy Colles’ fractures is associated with type 2 diabetes mellitus among postmenopausal women, irrespective of bone mineral density

Background

Recent meta-analysis data reveal that patients with type 2 diabetes mellitus (DM) have a higher risk of fracture, despite higher bone mineral density (BMD), than patients without type 2 DM. The purpose of this study was to compare BMD and distal radial shortening after low-energy Colles’ fractures among Japanese postmenopausal women aged ≥50 years with type 2 DM with those in women without it (non-DM).

Methods

One-hundred and ten postmenopausal women aged ≥50 years with distal radius fractures resulting from a fall were enrolled in this study. Twelve patients had DM. BMD, type I collagen cross-linked N-telopeptide (NTX), undercarboxylated osteocalcin (ucOC), estimated glomerular filtration rate (eGFR), grip strength of the unfractured hand, unipedal standing time, and the degree of radial shortening were measured.

Results

There were no significant differences in age and body height between the two groups. The DM group had significantly greater body weight and body mass index than the non-DM group. BMDs of the lumbar spine and proximal hip were significantly higher in the DM group than in the non-DM group. NTX, ucOC, grip strength, and the percentage of women with unipedal standing time <15 s did not differ between the two groups. Stepwise regression analysis identified DM and shorter unipedal standing time as significant factors associated with more radial shortening, and identified more radial shortening and lower eGFR as significant factors associated with DM.

Conclusions

More radial shortening after low-energy Colles’ fractures was significantly associated with type 2 DM among postmenopausal women aged ≥50 years, irrespective of BMD.     

The efficacy and safety of intravenous hydralazine for the treatment of hypertension in the hospitalized child

Background

Intravenous (IV) hydralazine is frequently used for the treatment of elevated blood pressure (BP) in hospitalized children. Its safety and efficacy have not been examined.

Methods

This is a retrospective chart review of IV hydralazine use in hospitalized children (birth to 17 years) over a 3-year period. Demographic data and data on adverse effects (AE), BP, and heart rate (HR) prior to and after each first dose were collected.

Results

The patient cohort comprised 110 children admitted to the hospital during the study period, of whom 77 received the recommended dose. Mean age of the children was 8.5?±?5.4 years; 33 % were male, and 32.5 % were white. Pre-dose systolic and diastolic BP indexes were 1.3 and 1.2, respectively. The median reduction in systolic and diastolic BP was 8.5 and 11.5 %, respectively. Sixteen (21 %) children achieved a 25 % reduction in systolic or diastolic BP, and BP increased in 30 % of patients; 10 % of children had a BP of <95th percentile for age, sex, and height after one dose. Seven (9 %) children had a documented AE. HR increased by a median of 3.5 %. In the multivariable models examining percentage change in systolic and diastolic BP, male gender was significantly associated with a change in systolic BP.

Conclusions

In hospitalized children, IV hydralazine was well tolerated, BP response was variable, and 21 % of the patients achieved a ≥25 % reduction of systolic or diastolic BP. Further studies are needed to compare the safety and efficacy of IV hydralazine to other short-acting antihypertensive agents.     

Impact of kidney function and urinary protein excretion on pulmonary function in Japanese patients with chronic kidney disease

Background

Although the cardiorenal relationship in chronic kidney disease has been investigated, information about the lung?kidney relationship is limited. Here, we investigated the impact of kidney function and urinary protein excretion on pulmonary dysfunction.

Methods

The data from pulmonary function tests and kidney function (estimated glomerular filtration rate [eGFR] and urinary protein) between 1 April 2005 and 30 June 2010 were selected from our laboratory database. Data were classified into 4 categories according to eGFR and proteinuria. Category 1, eGFR ≥60 ml/min/1.73 m² and urinary protein <0.3 g/gCr; category 2, eGFR <60 ml/min/1.73 m² and urinary protein <0.3 g/gCr; category 3, eGFR ≥60 ml/min/1.73 m² and urinary protein ≥0.3 g/gCr; and category 4, eGFR <60 ml/min/1.73 m² and urinary protein ≥0.3 g/gCr. Pulmonary function data were evaluated according to these 4 categories.

Results

A total of 133 participants without major respiratory disease, abnormal computed tomography and smoking history were enrolled. Hemoglobin (Hb)-adjusted percentage carbon monoxide diffusing capacity (%DL_CO) in category 4 (46.2 ± 7.5) and category 2 (63.6 ± 17.8) were significantly lower than in category 1 (75.8 ± 18.9) (P < 0.05). In addition, Hb-adjusted %DL_CO was weakly correlated with eGFR in participants with urinary protein <0.3 g/gCr (R = 0.30, P = 0.001). Hb-adjusted %DL_CO was strongly correlated with eGFR in participants with urinary protein ≥0.3 g/gCr (R = 0.81, P < 0.001). Other pulmonary function test markers (percentage (%) vital capacity, % forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, % total lung capacity, and % residual volume) were not significantly different between categories.

Conclusion

This study suggests that decreased eGFR is associated with decreased %DL_CO in proteinuric patients.     

Creatinine-based equations to estimate glomerular filtration rate in Japanese children aged between 2 and 11 years old with chronic kidney disease

Background

Renal inulin clearance is the gold standard for glomerular filtration rate (GFR), but is compromised by problems of collecting urine samples in children, especially those <6 years of age or with a bladder dysfunction. Therefore, we should utilize the serum creatinine (Cr)-based estimated GFR (eGFR), measuring serum Cr by enzymatic method. The updated Schwartz formulae were reported by enzymatic Cr instead of by the Jaffe method in American children aged 1–16 years old. We believe it would be better to determine serum Cr-based eGFR by the enzymatic method in Japanese children for evaluation of renal function.

Methods

Serum Cr-based eGFR was determined by measuring inulin clearance and serum Cr level in 76 pediatric chronic kidney disease (CKD) patients (49 males and 27 females) aged 2–11 years with no underlying disease that would affect renal function.

Results

We showed the inulin clearance by expression of the body length/serum Cr ratio in pediatric CKD patients, which resulted in the equation: $ {\text{inulin}}\;{\text{GFR}} = 0. 3 4 2 \times {\text{body length}}\;({\text{cm}})/{\text{serum}}\;{\text{Cr}}\;({\text{mg}}/{\text{dL}}) \pm 2. 7 5 $ . Additionally, we suggest the following serum Cr-based eGFR formula passing through the origin: $ {\text{eGFR}}\; ( {\text{mL}}/{ \hbox{min} }/ 1. 7 3 \,{\text{m}}^{ 2} )= 0. 3 5 \times {\text{body}}\;{\text{length}}\; ( {\text{cm)/serum}}\;{\text{Cr}}\; ( {\text{mg}}/{\text{dL)}} $ , because it is simple and easy to remember, thus making it clinically useful.

Conclusion

The new eGFR formula derived from body length and serum Cr level is applicable for clinical screening of renal function in Asian as well as Japanese children aged between 2 and 11 years old.     

Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease

Background

Renal inulin clearance is the gold standard for evaluation of kidney function, but cannot be measured easily in children. Therefore, we utilize the serum creatinine (Cr)-based estimated GFR (eGFR) measuring serum Cr by the enzymatic method, and we have reported simple serum Cr-based eGFR in Japanese children aged between 2 and 11 years old. Furthermore, we should use serum Cr-based eGFR in Japanese adolescents as well as children with chronic kidney disease for evaluation of renal function.

Methods

The inulin clearance and serum Cr level determined by an enzymatic method were measured in 131 pediatric chronic kidney disease (CKD) patients between the ages of 2 and 18 years old with no underlying disease affecting renal function except CKD to determine the serum Cr-based eGFR in Japanese children and adolescents.

Results

We offer the complex estimated GFR equation using polynomial formulae for reference serum creatinine levels with body length in Japanese children except infants, resulting in the following equation: $$ {\text{eGFR}} = 110.2 \times ({\text{reference serum Cr}}/{\text{patient's serum Cr}}) + 2.93 $$ Reference serum Cr levels (y) are shown by the following two equations of body length (x): $$ \begin{aligned} {\text{Males}}:\quad \, y = & -1.259x^{5} + 7.815x^{4} -18.57x^{3} + 21.39x^{2} -11.71x + 2.628 \\ {\text{Females}}:\quad \, y = & -4.536x^{5} + 27.16x^{4} -63.47x^{3} + 72.43x^{2} -40.06x + 8.778 \\ \end{aligned} $$

Conclusion

The new polynomial eGFR formula showing the relationship with body length and serum Cr level may be applicable for clinical screening of renal function in Japanese children and adolescents aged between 2 and 18 years.     

Sonographic evaluation of para- and perirenal fat thickness is an independent predictor of early kidney damage in obese patients

Purpose

To determine whether para- and perirenal fat ultrasonographic thickness (PFUT) is related to increased urinary albumin excretion and whether PFUT is an independent indicator of early kidney damage in obese subjects.

Method

Sixty-seven nonhypertensive, nondiabetic obese patients and 34 age- and sex-matched normal healthy volunteers were involved in this study. Clinical characteristics, blood biochemistry, PFUT, and urinary albumin/creatinine ratio (ACR) of the subjects were measured. The intraoperator and interoperator coefficient of variation was 5.6 and 3.2 %, respectively.

Results

ACR and PFUT were significantly higher in obese patients than those of normal healthy volunteers. PFUT was higher in obese patients with microalbuminuria than those with normoalbuminuria. Correlation analysis showed PFUT had a positive correlation with body mass index (BMI, r = 0.677, P < 0.01), waist circumference (WC, r = 0.686, P < 0.01), plasma free fatty acids (FFAs, r = 0.589, P < 0.01), and ACR (r = 0.610, P < 0.01). ACR had a positive correlation with BMI (r = 0.444, P < 0.01), WC (r = 0.440, P < 0.01), and plasma FFAs (r = 0.496, P < 0.01). Multivariate regression analyses showed that ACR could be predicted by PFUT.

Conclusions

PFUT may be an independent predictor of early kidney damage in nonhypertensive, nondiabetic obese patients, and PFUT could be a useful tool for the assessment of visceral fat and early kidney damage in obese patients.     

Urinary protein patterns in patients with Balkan endemic nephropathy

Purpose

Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls.

Methods

The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN.

Results

In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m² isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m², beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m² 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m² only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent.

Conclusion

Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m². IgG was increasingly found as eGFR decreased.     

Prevalence of chronic kidney disease risk factors among low birth weight adolescents

Background

By adulthood, low birth weight infants have an increased risk for chronic kidney disease (CKD). The extent to which objective CKD risk factors are present at earlier ages is unclear.

Methods

We analyzed 5352 participants aged 12–15 years in the National Health and Nutrition Examination Survey, 1999–2012. Participants were classified as low birth weight (LBW; < 2500 g), very low birth weight (VLBW; < 1500 g), or normal (2500–4000 g) by parental/proxy recall. Albuminuria (albumin/creatinine 30 – <300 mg/g), decreased estimated glomerular filtration rate (eGFR; < 90 ml/min/1.73 m²; Counahan–Barratt), and elevated systolic blood pressure (BP; ≥ 95th percentile for age, height, and sex) were considered CKD risk factors.

Results

While albuminuria did not vary by birth weight, elevated blood pressure (BP) and decreased eGFR occurred more frequently in LBW/VLBW adolescents (elevated BP: LBW 6.0 %, VLBW 11.2 %, normal 2.4 %; decreased eGFR: LBW 23.2 %, VLBW 32.5 %, normal 16.1 %). After multivariable adjustment, LBW/VLBW adolescents had greater odds for both elevated BP (LBW: OR 2.90, 95 % CI 1.48–5.71; VLBW: 5.23; 1.11–24.74) and decreased eGFR (LBW: 1.49, 95 % CI 1.06–2.10; VLBW 2.49, 95 % CI 1.20–5.18).

Conclusions

In the U.S. population, both decreased eGFR and elevated systolic BP occur frequently among adolescents with history of LBW/VLBW.

     

Skin autofluorescence as a marker of cardiovascular risk in children with chronic kidney disease

Background

We examined skin autofluorescence (sAF) in chronic kidney disease children (CKD) in relation to renal function and dialysis modality.

Methods

Twenty children on hemodialysis (HD), 20 on peritoneal dialysis (PD), 36 treated conservatively, and 26 healthy subjects were enrolled into the study. In all children sAF, pulse-wave velocity indexed to height (PWV/ht), left ventricular mass index (LVMI), blood pressure (BP), serum lipid profile, phosphate (P), calcium (Ca), and homocysteine were measured.

Results

sAF was significantly elevated in CKD groups vs. controls and was significantly associated with PWV/ht, LVMI, BP, P, Ca?×?P product and homocysteine. sAF in HD and PD groups was positively correlated with dialysis vintage, and in the predialysis group negatively correlated with glomerular filtration rate (eGFR). Multiple regression analysis showed significant association of sAF with LVMI and P in the CKD patient group, and with dialysis treatment duration and BP in dialyzed children.

Conclusions

In CKD children, tissue accumulation of advanced glycation end-products (AGEs) was observed. This was aggravated as eGFR declined and was related to early cardiovascular changes and some biochemical cardiovascular disease (CVD) risk markers. sAF as a non-invasive method may be a useful tool for identification of a clinical risk factors of cardiovascular disease in CKD children.     

Limited value of routine microalbuminuria assessment in multi-ethnic obese children

Background

To determine the prevalence of microalbuminuria and its association with cardiometabolic risk factors in a multi-ethnic cohort of overweight and obese children.

Case-Diagnosis/Treatment

A retrospective analysis of prospectively collected data was performed using data from 408 overweight and obese children (age 3–19 years). In addition to administering an oral glucose tolerance test, we measured anthropometric variables, plasma lipid levels, alanine aminotransferase and the urinary albumin/creatinine ratio (ACR). Microalbuminuria was defined as an ACR of between 2.5 and 25 mg/mmol in boys and 3.5 and 25 mg/mmol in girls. In total, only 11 (2.7 %) of the children analyzed presented with microalbuminuria, with no differences between ethnic groups, sex or in the prevalence of hypertension compared to the children with normoalbuminuria. After adjustment for confounders, the body mass index Z-score tended to be different between the group with microalbuminuria versus that without (3.6 vs. 3.2, respectively; P?=?0.054). ACR was not associated with hypertension, impaired glucose tolerance, high triglycerides or low high-density lipoprotein-cholesterol.

Conclusions

In a large multi-ethnic cohort of overweight and obese children, we found a low prevalence of microalbuminuria (11 children, 2.7 %), and in this small number of individuals, we found no association with any of the cardiometabolic risk factors assessed. Therefore, our data do not support the routine measurement of microalbuminuria in asymptomatic overweight and obese children and adolescents.     

Thyroid hormone replacement therapy for primary hypothyroidism leads to significant improvement of renal function in chronic kidney disease patients

Background

The interactions between kidney and thyroid functions have been known for many years; however, there are few studies on the extent of the improvements and long-term changes of renal function after thyroid hormone replacement therapy (THRT) in chronic kidney disease (CKD) patients. The purpose of this study was to determine how THRT affects the estimated glomerular filtration rate (eGFR) in CKD patients with primary hypothyroidism.

Methods

A retrospective investigation was performed on 51 Japanese patients (15 men and 36 women) with primary hypothyroidism. The changes in eGFR after THRT were examined according to the existence of CKD and severity of thyroid function.

Results

eGFR increased rapidly over the first 6 months after THRT in CKD patents, which was followed by a plateau. There was a correlation between eGFR and the severity of hypothyroidism, which was independent of age, and eGFR in severely hypothyroid patients significantly increased up to levels that were similar to mildly hypothyroid patients after THRT. eGFR improved more in the lower initial eGFR group and increased about 30 % in CKD patients (47.5 ± 7.7 vs. 62.1 ± 9.5 ml/min/1.73 m², P < 0.01). Moreover, eGFR in CKD patients with mild to moderate hypothyroidism was significantly increased compared to that in non-CKD patients.

Conclusion

Our data suggested that hypothyroidism contributed to the reduction in eGFR, especially in CKD patients; therefore, patients with CKD should positively be examined for thyroid function, and appropriate THRT should be started if needed.