Elevated systolic blood pressure in preterm very-low-birth-weight infants ��3 years of life

Preterm, very-low-birth-weight neonates (≤1500 gm, VLBW) exhibit elevated systolic blood pressures (SBP) in adolescence and adulthood; however, the age of onset and causes are unknown. We assessed SBP in a cross-sectional study of VLBW infants at 1, 2 and 3 years of age (n = 40 per cohort). SBP was manually measured using Doppler amplification (observed), and calm values were compared to reference ranges used for clinical purposes (expected). SBP was converted to age-, gender- and height-specific z-scores (SBPz). Perinatal variables and growth parameters measured between 6 and 36 months were assessed as predictors of an elevated SBP. Observed SBP and SBPz exceeded the expected value at each age (P < 0.01); for example 1 year SBP was 94 ± 10 (standard deviation) vs. 85 ± 3 mmHg, respectively. Although the expected SBP rose from 85 ± 3 to 90 ± 3 mmHg with advancing age (P < 0.05), VLBW SBP was unchanged (P > 0.1), averaging 93 mmHg across ages. Height and weight z-scores were below expected (P < 0.01), while weight-for-height z-scores exceeded zero at 6, 12 and 24 months (P < 0.05). Male subscapular skinfold thickness:abdominal circumference ratio decreased with advancing age, paralleling the decreases in SBPz. The VLBW neonates demonstrated an elevated SBP as early as 1 year of age. Although predictive perinatal variables were not identified, gender-specific relationships between infant growth and SBP were observed.     

Chronic hemodialysis in infants and children under 2 years of age

Over the past 16 years, 18 children under 2 years of age received chronic hemodialysis (HD) at our center. Five children were anuric at the start of HD and 6 had significant co-morbidity. The most common underlying diagnosis was posterior urethral valves. The median age at the start of HD was 12.2 months. A total of 39 episodes (defined as a discrete time period during which HD was the principle form of renal replacement therapy) of HD were performed, with a median duration of 7 months and 91.3 dialysis sessions per episode. Problems with vascular access were very common, with a revision ratio of 40%. Twenty-two line revisions were required for 36 episodes of line infection, with a median rate of line infection of 2.7 infections/patient years. The most commonly encountered organism was coagulase-negative Staphylococcus (69%). Twenty-three lines needed revision due to poor line function, despite the routine use of heparin. The effectiveness of HD was assessed in 11 patients who received HD for a continuous period of 3 or more months. The median urea reduction rate was 72%, while the parathyroid hormone levels improved to within twice the upper limit of the reference range in 69%. While there was no significant change in the median weight and height standard deviation score (SDS), the median SDS for head circumference showed significant improvement ( P=0.04). Both growth and developmental outcomes were strongly influenced by existing co-morbidity. Sixteen (89%) children were transplanted. Four (22%) children died, 3 after successful transplants. None of the deaths occurred on HD or resulted from its complications. In conclusion, HD in infants and small children is an effective and safe form of renal replacement therapy, but problems with vascular access limit its long-term use.     

Renal phosphate handling of premature infants of 23–25 weeks gestational age

Premature infants with low serum phosphate concentrations (<2 mmol/l) are at risk for osteopenia. Therefore, serum phosphate levels in premature infants should be kept above 2 mmol/l. Premature infants of 26-31 weeks gestational age (GA) have renal phosphate threshold concentrations (Tp/GFR) in the range of normal serum phosphate values (2 mmol/l). Therefore, these infants show significant urinary phosphate excretion only when serum phosphate levels are normal, and urinary phosphate excretion can be used to monitor phosphate supplementation. However, few data are available on extremely premature infants of 23-25 weeks GA. The objective of this study was to compare Tp/GFR levels in infants of 23-25 weeks GA to those in infants of 26-31 weeks GA. We retrospectively evaluated case notes of 12 infants of 23-25 weeks GA and compared them to 19 infants of 26-31 weeks GA. Tp/GFR was calculated from simultaneous measurements of urinary phosphate, urinary creatinine, serum phosphate, and serum creatinine. Tp/GFR values 3-5 weeks postnatally were lower in infants of 23-25 weeks GA (1.06+/-0.36 mmol/l, p<0.001) than in infants of 26-31 weeks GA (1.76+/-0.26 mmol/l). Near term (35-37 weeks postmenstrual age), there was no significant difference between Tp/GFR values in infants of 23-25 weeks GA (1.83+/-0.32 mmol/l) and in infants of 26-31 weeks GA (2.05+/-0.22 mmol/l). We conclude that at 3-5 weeks postnatally, infants of 23-25 weeks GA are at risk for low Tp/GFR values, leading to urinary phosphate excretion even in the presence of low serum phosphate levels. In these infants, serum phosphate levels should be monitored, and phosphate supplementation should be adjusted to keep serum phosphate levels above 2 mmol/l.     

Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age

Background

There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls).

Methods

The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years.

Results

The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m², respectively, at 7 years (p <0.01) and 51.4 vs. 58.2 ml/m², respectively, at 11 years (p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m², respectively, at 7 years (p <0.01) and 55.2 vs. 60.7 ml/m², respectively, at 11 years (p?=?0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years (p?=?0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years (p?=?0.01)]. Six ELBW children also had elevated cystatin C levels (0.97–1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p?=?0.028).

Conclusion

Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood.

     

Renal cell carcinoma in adults less than 40 years of age: a particular cancer? Incidence,outcome and review of the literature

OBJECTIVE: To study the incidence, clinical presentation, pathological prognostic factors and disease outcome of RCC in young adults less than 40-years-old. MATERIAL AND METHODS: The notes of 400 patients treated by radical nephrectomy for RCC suspicion, between January 1984 and december 1999 were reviewed. Twenty-nine patients (7.25%) were under 40. RESULTS: The most common histological cell type was clear cell carcinoma, found in 20 patients (69%). At a median follow-up of 80 months, 20 patients (69%) were disease free and 9 (31%) died of the disease. When comparing patients less than 40 years vs older than 40 years, we found significant differences in histology type (clear cell carcinoma 69% vs 91%; P = 0.0001), and tumor stage at presentation (pT2 = 34.5% vs 17.3%; P = 0.04) (pT3 = 20.7% vs. 42%; P = 0.03). Disease free survival was not significantly different between the 2 groups (69% vs 65.7%; Log rank test P = 0.4). CONCLUSION: Although rare, RCC in young adults seems to follow a course similar to the disease seen in older patients. Stage at presentation was different between the 2 populations however survival was not affected by age.     

Associations between hypothalamic–pituitary–adrenal axis function and peak bone mass at 20 years of age in a birth cohort

In older adults, high-normal circulating cortisol levels are associated with lower bone mass, but relationships between hypothalamic–pituitary–adrenal axis function and peak bone mass in young adults have not been examined. We studied 411 male and 390 female participants in the Western Australia Pregnancy Cohort (Raine) Study. At 18 years of age, participants underwent a Trier Social Stress Test (TSST) with measurement of plasma and salivary cortisol at baseline and at multiple time points after stress. Cortisol responses were classified as anticipatory responder (significant fall in cortisol during the test), reactive responder (significant increase) or non-responder. At 20 years, total body bone mineral content (BMC) and density (BMD) were measured by DXA. In males, after adjustment for weight, height (for BMC and bone area only), alcohol and smoking, there was a significant inverse relationship between both plasma and salivary cortisol measured at baseline in the TSST and each of BMC and BMD, such that each additional 10% of salivary cortisol was associated with reductions of 6.9 g (95% CI − 11.7, − 2.2) in BMC, and 1.8 mg/cm² (95% CI − 3.3, − 0.4) in BMD. Males classified as anticipatory responders in the TSST had 3.2% lower BMC (adjusted mean ± SE: 3131 ± 28 vs. 3233 ± 18 g, P = 0.006) and 2.5% lower BMD (1108 ± 9 vs. 1136 ± 6 mg/cm², P = 0.022) than reactive responders. In females, there were no significant relationships between baseline cortisol or TSST responses and BMC or BMD in covariate-adjusted analyses. We conclude that in young males (but not females), higher circulating cortisol at the baseline of the stress test and an anticipatory responder pattern on the TSST are associated with lower total body bone mass.     

Evaluation of excess skin in Swedish adults 18–59 years of age

Background: Little is known about excess skin in the normal population. The aim of this study was, therefore, to analyse the prevalence, impairments, and discomfort of excess skin in a cross-section of the Swedish population.

Methods: From the population registry of the Swedish Tax Agency, 1408 subjects living in Västra Götaland County from 18–59 years of age were randomly selected with an equal distribution of the sexes. Additionally, age was equally distributed, although twice as many subjects under 40 years of age were sent the questionnaire due to an expected low response rate for younger people. All subjects were asked to fill out the Sahlgrenska Excess Skin Questionnaire (SESQ), which included questions concerning the amount of and discomfort due to excess skin.

Results: No excess skin was reported by 78% of responders, including 71% of women and 87% of men. The responders who reported any excess skin were significantly older, had a higher body mass index (BMI) and reported larger differences between their maximum and current BMI. The most common reported site of excess skin was the abdomen in both women and men (26% and 8%, respectively), and this was reported to cause the most discomfort (median 4 and 2, respectively, on a scale from 0–10). Women graded psychosocial symptoms significantly higher than men, but there were no significant differences in other symptoms.

Conclusions:The results indicate that Swedish adults, regardless of sex, do not suffer from excess skin and may be considered as reference values.     

Ambulatory blood pressure monitoring in living kidney donors: What changes in 10 years?

In renal transplantation, living donations have more significant benefits compared to cadaveric donations. However, a probable increase in blood pressure following donation should also be kept in mind. In this study, we investigated the long‐term changes in blood pressure in living kidney donors using ambulatory blood pressure monitoring and we explored the e‐GFR and albuminuria/proteinuria measurements at 3 time points. Twenty‐eight living kidney donors and 39 healthy individuals were evaluated and compared at the baseline and later at the 10th year. At the 10th year, creatinine levels were higher and eGFR levels were lower in the donors, whereas the systolic and diastolic measurements of the donors and controls and the prevalence of nondipping in the donors and controls were similar. Our study may be underpowered due to its small population size. However, our results at the 10th year follow‐up indicated that the risk of hypertension might not seem to have increased in the well‐selected donors. In addition, the majority of our donors had preserved their GFR values. Therefore, we can suggest that living kidney donation appears to be safe in well‐selected patients over a 10‐year time frame.     

Long-term follow-up of ACE-inhibitor versus β-blocker treatment and their effects on blood pressure and kidney function in renal transplant recipients

Hypertension and nephrotoxicity are frequent complications of cyclosporine-induced immunosuppression in renal transplant recipients. Long-term antihypertensive treatment is obligatory for hypertensive transplant patients, to protect allograft function. The use of angiotensin-converting enzyme (ACE) inhibitors in the anti-hypertensive treatment of renal transplant recipients who receive immunosuppression with cyclosporine has long been discussed controversially. The aim of this prospective study, with a duration of 2 years and a follow-up of another 3 years, was to estimate the long-term antihypertensive potential of quinapril compared with that of the beta-blocker atenolol and to compare their effects on renal allograft function and proteinuria in 96 hypertensive renal transplant recipients who received cyclosporine A as immunosuppressive therapy. Patients were randomly assigned to receive either quinapril (group Q) or atenolol (group A) as anti-hypertensive treatment. Forty patients of each group completed the 5-year observation period according to protocol. Intention-to-treat and according-to-protocol analyses were performed. With the patients starting at similar baseline blood pressure values, both agents, atenolol and quinapril, decreased systolic and diastolic blood pressure (SBP, DBP) as well as middle arterial pressure (MAP) and pulse pressure (PP) to a similar extent (Delta SBP: group Q: -8+/-3 vs group A mmHg: -5+/-3; Delta DBP: -5+/-2 vs -4+/-2 mmHg; Delta MAP: -6+/-2 vs -5+/-2 mmHg; Delta PP: -2+/-2 vs -1+/-3 mmHg; mean +/- SEM). Neither serum creatinine levels nor Cockcroft-Gault clearance had changed significantly in either group after the 5-year period (Delta creatinine: 0.1+/-0.1 vs 0.2+/-0.2 mg/dl; Delta Cockcroft-Gault clearance: 3.9+/-4.6 vs 2.8+/-4.3 ml/min; mean +/- SEM). Urinary protein excretion remained stable among the quinapril-treated patients, whereas a significant increase was observed in the atenolol group during the 5-year study period (group Q: from 0.52+/-0.08 to 0.54+/-0.14 g/24 h; group A: from 0.34+/-0.03 to 0.72+/-0.13 g/24 h, P<0.02; mean +/- SEM). Albuminuria increased comparably in both groups, while the excretion of alpha-microglobuline increased slightly in the atenolol group, but decreased slightly in the quinapril group. The difference between the groups failed to be statistically significant (ANOVA, P<0.056). In conclusion, quinapril and atenolol may be considered suitable and safe substances in the long-term treatment of hypertensive renal transplant recipients, since both agents prove to be effective in anti-hypertensive treatment, and keep allograft function stable over a period of 5 years.     

Discrepancies in office and ambulatory blood pressure in adolescents: help or hindrance?

The goal of this commentary is to review the most relevant topics concerning the clinical utility of ambulatory blood pressure (BP) monitoring, such as the state of the art “reference BP values”, the importance of the discrepant situations between office and ambulatory BP (white-coat and masked hypertension) and those of the recommended clinical indications to now. From a small number of studies, operational thresholds to define hypertension have been established. They are useful tools even though more studies are necessary to create strong reference values. Ambulatory BP measurement is increasingly recognized as being indispensable to the diagnosis and management of hypertension, and it has contributed significantly to our understanding of hypertension by revealing or “unmasking” BP phenomena that were not readily apparent using traditional techniques of measurement in clinical practice. Ambulatory BP monitoring should be performed in adolescents with either office mild essential hypertension before starting antihypertensive drug treatment or a strong family history of hypertension or an early cardiovascular event. Obese children with normal office BP values will also benefit from ambulatory BP monitoring. Other indications are the assessment of refractory hypertension or drug-induced hypotension. Finally, additional BP information in chronic renal failure, diabetes, and autonomic neuropathy can be obtained by using ambulatory BP monitoring None of the authors has a conflict of interest to declare. The corresponding author had final responsibility for the decision to submit for publication.     

ABO-incompatible kidney transplantation in elderly patients over 60?years of age

Introduction

Patients aged 60?years and older represent the fastest-growing population with end-stage renal disease worldwide, and the need for a kidney transplant among this population is increasing. Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved, and the rates of graft survival in these patients are currently similar to those in recipients of ABO-compatible grafts. However, the outcomes of ABO-incompatible kidney transplantation in elderly patients over 60?years of age have not been well studied yet.

Patients and methods

We studied 4 elderly kidney transplant patients who received their grafts from ABO-incompatible living donors at our institution between December 2006 and December 2011, focusing on the immunosuppressive protocols, complications and graft survivals. The mean observation period was 21.5?months (range, 8?months to 62?months). Our immunosuppressive protocols were as follows: to remove the anti-A/B antibodies, the patients underwent 4?C8 sessions of double-filtration plasmapheresis and/or plasma exchange prior to kidney transplantation until the anti-A/B titers were less than 1:16. For the patients with low anti-A/B titers (<1:512), the immunosuppressive protocol consisted of a single dose of rituximab (150?mg/m²). The patients with high anti-A/B antibody titers (??1:512) underwent splenectomy and received 2 doses of rituximab. The pretransplant immunosuppressive protocol included B-lymphocyte suppression with 4?weeks of mycophenolate mofetil (0.5?g/day for low-titer protocol and 1?g/day for high-titer protocol).

Results

All 4 patients underwent successful transplantation. At the end of follow-up, their mean serum creatinine was 1.18?mg/dl. No patient experienced antibody-mediated rejection or acute cellular rejection. Late-onset neutropenia occurred in two cases. Two cases experienced cytomegalovirus reactivation by cytomegalovirus antigenemia. In one patient, diffuse hemorrhage required surgical intervention. However, there were no severe complications.

Conclusions

Although a careful evaluation of patients is needed, ABO-incompatible kidney transplantation may become a viable treatment option for elderly patients with end-stage renal disease.     

The impact of circulation in a heart–lung machine on function and survival characteristics of red blood cells

Extracorporeal circulation is accompanied by changes in red blood cell morphology and structural integrity that affect cell function and survival, and thereby may contribute to the various side effects of heart–lung machine-assisted surgery. Our main objectives were to determine the effect of circulation of red blood cells in a stand-alone extracorporeal circuit on several parameters that are known to be affected by, as well as contribute to red blood cell aging. As a source of RBCs, we employed blood bank storage units of different ages. In order to assess the relevance of our in vitro observations for the characterization of extracorporal circulation technology, we compared these changes in those of patients undergoing extracorporeal circulation-assisted cardiac surgery. Our results show that circulation in a heart–lung machine is accompanied by changes in red blood cell volume, an increase in osmotic fragility, changes in deformability and aggregation behavior, and alterations in the exposure of phosphatidylserine and in microvesicle generation. RBCs from 1-week-old concentrates showed the highest similarities with the in vivo situation. These changes in key characteristics of the red blood cell aging process likely increase the susceptibility of red blood cells to the various mechanical, osmotic, and immunological stress conditions encountered during and after surgery in the patient’s circulation, and thereby contribute to the side effects of surgery. Thus, aging-related parameters in red blood cell structure and function provide a foundation for the validation and improvement of extracorporeal circulation technology.