Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin.

In an attempt to clarify the mechanisms of post-transplant bone disease we investigated the bone content and gene expression of several bone-related proteins. After a successful kidney transplant, the content of sclerostin in bone biopsies was found to be increased as measured by immunohistochemistry, multiplex assay, and gene expression despite a concomitant decrease of sclerostin in the serum. The phosphorylation of beta-catenin was increased, confirming Wnt pathway inhibition, an effect accompanied by an increase of the receptor activator of nuclear factor kappa-Β ligand (RANKL) and a decrease of osteoprotegerin protein levels in both serum and bone. Thus, changes in circulating biomarkers after kidney transplantation cannot be easily extrapolated to concomitant changes occurring in the bone. Hence, overall treatment decisions post kidney transplant should not be based on serum biochemistry alone.

Growth in children with chronic kidney disease and associated risk factors for short stature.

INTRODUCTION: Growth failure in chronic kidney disease is related to high morbidity and mortality. Growth retardation in this disease is multifactorial. Knowing the modifiable factors and establishing strategies to improve care for affected children is paramount. OBJECTIVES: To describe growth patterns in children with chronic kidney disease and the risk factors associated with short stature. METHODS: We retrospectively analyzed anthropometric and epidemiological data, birth weight, prematurity, and bicarbonate, hemoglobin, calcium, phosphate, alkaline phosphatase, and parathormone levels of children with stages 3-5 CKD not on dialysis, followed for at least one year. RESULTS: We included 43 children, the majority of which were boys (65%). The mean height/length /age z-score of the children at the beginning and follow-up was -1.89 ± 1.84 and -2.4 ± 1.67, respectively (p = 0.011). Fifty-one percent of the children had short stature, and these children were younger than those with adequate stature (p = 0.027). PTH levels at the beginning of the follow-up correlated with height/length/age z-score. A sub-analysis with children under five (n = 17) showed that 10 (58.8%) of them failed to thrive and had a lower weight/age z-score (0.031) and lower BMI/age z-score (p = 0.047). CONCLUSION: Children, particularly younger ones, with chronic kidney disease who were not on dialysis had a high prevalence of short stature. PTH levels were correlated with height z-score, and growth failure was associated with worse nutritional status. Therefore, it is essential to monitor the growth of these children, control hyperparathyroidism, and provide nutritional support.

Dialysis-related thrombocytopenia: a case report.

Thrombocytopenia is frequently observed in hemodialysis patients, and its correct investigation and control remain a challenge. It is estimated that during the hemodialysis session there is a drop of up to 15% in the platelet count, with recovery after the end of treatment. This reduction in platelets is due to platelet adhesion and complement activation, regardless of the membrane material. Several studies with platelet surface markers demonstrate increased platelet activation and aggregation secondary to exposure to cardiopulmonary bypass. This case report describes a patient on hemodialysis who developed severe thrombocytopenia during hospitalization. Investigation and exclusion of the most common causes were carried out: heparin-related thrombocytopenia, adverse drug reaction, hypersplenism, and hematological diseases. Afterwards, the possibility of hemodialysis-related thrombocytopenia was raised, since the fall was accentuated during the sessions with partial recovery after the dialyzer change. Attention to the sterilization method and dialyzer reuse must be considered for correction. In the current case, reusing the dialyzer minimized the drop in platelet counts associated with hemodialysis.

Obstetric outcome in pregnant women on long-term dialysis: a case series.

BACKGROUND: Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. STUDY DESIGN: Retrospective case series. SETTING & PARTICIPANTS: Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the São Paulo University Medical School (São Paulo, Brazil). OUTCOMES & MEASUREMENTS: We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. RESULTS: 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P < 0.001), lower gestational age (P < 0.001), and birth weight (P < 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P < 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. LIMITATIONS: Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. CONCLUSIONS: Outcomes of pregnancy in women undergoing hemodialysis often are good. Pre-eclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight.

Dialysis-related thrombocytopenia: a case report / Plaquetopenia relacionada à hemodiálise: relato de caso

Abstract Thrombocytopenia is frequently observed in hemodialysis patients, and its correct investigation and control remain a challenge. It is estimated that during the hemodialysis session there is a drop of up to 15% in the platelet count, with recovery after the end of treatment. This reduction in platelets is due to platelet adhesion and complement activation, regardless of the membrane material. Several studies with platelet surface markers demonstrate increased platelet activation and aggregation secondary to exposure to cardiopulmonary bypass. This case report describes a patient on hemodialysis who developed severe thrombocytopenia during hospitalization. Investigation and exclusion of the most common causes were carried out: heparin-related thrombocytopenia, adverse drug reaction, hypersplenism, and hematological diseases. Afterwards, the possibility of hemodialysis-related thrombocytopenia was raised, since the fall was accentuated during the sessions with partial recovery after the dialyzer change. Attention to the sterilization method and dialyzer reuse must be considered for correction. In the current case, reusing the dialyzer minimized the drop in platelet counts associated with hemodialysis.

Resumo Plaquetopenia é frequentemente observada em pacientes em hemodiálise, e sua correta investigação e controle permanecem um desafio. Estima-se que, durante a sessão de hemodiálise, ocorra queda de até 15% da contagem de plaquetas, com recuperação após o término do tratamento. Essa queda de plaquetas é decorrente de adesão plaquetária e ativação do complemento, independentemente do material da membrana. Vários estudos com marcadores de superfície plaquetária demonstram aumento da ativação e agregação plaquetária secundários à exposição à circulação extracorpórea. Este relato de caso mostra um paciente dialítico que evoluiu com plaquetopenia severa durante internação. Realizada investigação e exclusão de causas mais comuns: plaquetopenia relacionada à heparina, reação adversa a medicamentos, hiperesplenismo e doenças hematológicas, foi então aventada a possibilidade de plaquetopenia relacionada à hemodiálise após observação de que a queda se acentuava durante as sessões de hemodiálise com recuperação parcial após. Mudança do dialisador, atenção ao método de esterilização e realização do reuso devem ser consideradas para correção. No presente caso, a utilização do reuso minimizou a plaquetopenia associada a hemodiálise.

Positive acute-phase inflammatory markers in different stages of chronic kidney disease.

BACKGROUND: An elevated serum level of acute-phase inflammatory markers is associated with an increased risk of cardiovascular disease. We hypothesized that elevated acute-phase inflammatory markers are directly associated with the different stages of chronic kidney disease (CKD). METHODS: We evaluated the relationship between serum levels of high-sensitivity C-reactive protein (hsCRP) and alpha1-acid glycoprotein (alpha1-AGP), as well as the renal function in 224 adult patients with CKD (mean age 56.6 years, 46% male, and 40% diabetics), stratified according to the glomerular filtration rate (GFR) (based on the National Kidney Foundation/Kidney Dialysis Outcomes Quality Initiatives), and in 94 hemodialysis patients. RESULTS: The mean hsCRP was 8.2 +/- 12.1 mg/l, and hsCRP levels were >5 mg/l in 44.4% of the patients; alpha1-AGP levels were >125 mg/dl in 33.3% of the patients. Mean hsCRP and alpha1-AGP were significantly higher in more severe stages of CKD. A weak inverse relationship was found between GFR and serum hsCRP (r = -0.2205; p = 0.0006) and between GFR and serum alpha1-AGP (r = -0.3266; p < 0.0001). There was a correlation between hsCRP and alpha1-AGP (r = 0.3417; p < 0.0001). No significant differences were detected between patients with CKD and those undergoing hemodialysis concerning hsCRP (8.2 +/- 12.1 vs. 6.8 +/- 7.4 mg/l; p = 0.2980) and alpha1-AGP (116.3 +/- 42.5 vs. 117.2 +/- 37.9 mg/dl; p = 0.8590). However, the level of hsCRP was significantly reduced in hemodialysis patients compared with patients with stage 5 predialytic disease (12.1 +/- 13.9 to 6.8 +/- 7.4 mg/l; p = 0.005). More patients with stage 5 predialytic CKD had an elevated hsCRP serum level compared with patients on hemodialysis (64.7 vs. 37.9%; chi2 = 6.230, p < 0.01). CONCLUSIONS: Approximately 50% of patients with CKD--even in the early phase of renal failure--exhibit an activated acute-phase response, which is closely related to the stages of CKD. Hemodialysis may partially correct the inflammatory process present in the immediate predialysis phase of CKD.