Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.     

TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring

Background

In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children.

Methods

The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels.

Results

There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism.

Conclusions

Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.     

Early inhibition of the renin‐angiotensin system improves the long‐term graft survival of single pediatric donor kidneys transplanted in adult recipients

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin‐angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996–2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan–Meier estimated death‐censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33–5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18–0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long‐term graft survival among adults transplanted with single pediatric donor kidneys.     

Simple preoperative parameters to assess technical difficulty during a radical perineal prostatectomy

Purpose

We aimed to propose a practical selection method predicting the easier radical perineal prostatectomy (RPP) cases before the operation.

Methods

Fifty sequential RPP cases were divided into two groups according to the estimated difficulty of the operation (Group I: Easier, Group II: Difficult) which was assessed by using a RPP difficulty scale, constituted by three parameters (operation time, blood loss, and the judgment of the surgeon) each ranging between 1 and 3 points. As the localization parameters, skin-to-prostatic apex (SPAD) and skin-to-prostatic base (SPBD) distances and distance between bilateral ischial tuberosities (ITD) were measured. During suprapubic ultrasonography, a probe-divergence angle (PDA) and prostate volumes (PV) were recorded. These parameters were compared between the groups.

Results

In Group I (n = 29) and Group II (n = 21), the difficulty scores were 4.37 (3–5) and 6.80 (6–9), respectively. Data of age, clinical stages, and findings of digital rectal examination were not different between groups. While SPBD, SPAD, and ITD values were found similar (p > 0.05), PDA and PV were significantly different. PDA was > 45 degree in 21 cases in Group I (72.4 %) and in 7 cases in Group II (33.3 %) (p = 0.011). The mean of PV was 37.4 (20–60) cc and 49.9 (30–75) cc in Group I and Group II, respectively (p = 0.001).

Conclusions

While planning RPP operations, by selecting the prostate cancer cases with a prostate of low volume and localized deeper in the pelvis during suprapubic ultrasonography, urologists may have a chance to perform this technique more easily during the learning period.     

A Case of Kaposi's Sarcoma Following Treatment of Membranoproliferative Glomerulonephritis and a Review of the Literature

Kaposi's sarcoma (KS) is an unusual tumor principally affecting the skin of the lower extremities. Although the association between KS and renal transplant has been well documented, there are a few KS cases in the literature associated with membranoproliferative glomerulonephritis or other glomerular diseases. This report presents a patient with membranoproliferative glomerulonephritis (MPGN) who developed KS following treatment with long-term medium dose glucocorticoid and short-term additional immunosuppressives. The KS cases associated with glomerulonephritis are also reviewed. KS is a rare complication in glomerular diseases that may (or may not) be related to immunosuppression. Hence, immunosuppression treatment should be carefully planned in glomerulonephritis treatment and avoided if they are not essentially necessary.     

“Walking with Only Non-Invasive Ventilation in Stable Hypercapnic COPD Patients: Sufficient or Not?”

We are grateful to Ulasli and Esquinas for their comments to our paper.. They argued that arterial blood gas analyses were not performed without oxygen prior to the 6-minute walk test with noninvasive ventilation (6MWT-NPPV). This point has already been discussed in our original work by indicating the limitations of our study. The reason for using oxygen prior to exercise testing was to guarantee comparable starting conditions.