A comparison of laboratory values in pediatric hemodialysis patients: does day of the week matter?

BACKGROUND: The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-K/DOQI) guidelines recommend the delivered dose of hemodialysis (HD) be measured no less than monthly by checking Kt/V (K is effective urea clearance, t is minute and V is urea distribution). To date, no studies have explored whether the day of the week for checking maintenance HD laboratory studies impacts dialysis dosing. METHODS: Data were collected at two HD facilities on 19 patients, ages ≤ 21 years receiving maintenance HD thrice weekly over a consecutive 6-month period. Data obtained from the Monday and Wednesday of each full third week of the month included dialysis vintage, ultrafiltration volume, serum electrolytes, hemoglobin and clearances. RESULTS: Kt/V and K+ were significantly different between Monday and Wednesday (P = 0.013 and P = 0.047, respectively). CONCLUSION: Due to variability in values based on the day of laboratory evaluations, the dialysis provider must consider the impact of this on the quality of patient care when prescribing dialysis. Research on a larger scale needs to be conducted to allow for better decision-making capabilities in the chronic HD population.

Evaluation of Proteinuria and Hematuria in Ambulatory Setting.

Proteinuria and/or hematuria are common findings in ambulatory settings. Proteinuria can be glomerular and/or tubular in origin and it may be transient, orthostatic, or persistent. Persistent proteinuria may be indicative of a serious kidney pathology. Hematuria, which denotes the presence of an increased number of red blood cells in the urine, can be gross or microscopic. Hematuria can originate from the glomeruli or other sites of the urinary tract. Asymptomatic microscopic hematuria or mild proteinuria in an otherwise healthy child is less likely to be of clinical significance. However, the presence of both requires further workup and careful monitoring.

Hypernatremia in Newborns: A Practical Approach to Management.

Hypernatremia is a potentially serious condition in both term and preterm babies, which can lead to severe and permanent neurological damage. There are many physiological changes in sodium homeostasis that occur soon after birth. Understanding this physiological process, early anticipation of hypernatremia and familiarization with the neonatal management of hypernatremia can prevent mortality and long-term morbidity associated with this condition. This review aims to provide a practical and understandable approach to the diagnosis and management of hypernatremia in neonates.

A Multicenter Study Evaluating the Discontinuation of Eculizumab Therapy in Children with Atypical Hemolytic Uremic Syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA), which has been treated successfully with eculizumab. The optimal duration of eculizumab in treating patients with aHUS remains poorly defined. METHODS: We conducted a multicenter retrospective study in the Arabian Gulf region for children of less than 18 years of age who were diagnosed with aHUS and who discontinued eculizumab between June 2013 and June 2021 to assess the rate and risk factors of aHUS recurrence. RESULTS: We analyzed 28 patients with a clinical diagnosis of aHUS who had discontinued eculizumab. The most common reason for the discontinuation of eculizumab was renal and hematological remission (71.4%), followed by negative genetic testing (28.6%). During a median follow-up period of 24 months after discontinuation, 8 patients (28.5%) experienced HUS relapse. The risk factors of recurrence were positive genetic mutations (p = 0.020). On the other hand, there was no significant relationship between the relapse and age of presentation, the need for acute dialysis, the duration of eculizumab therapy before discontinuation, or the timing of eculizumab after the presentation. Regarding the renal outcomes after discontinuation, 23 patients were in remission with normal renal function, while 4 patients had chronic kidney disease (CKD) (three of them had pre-existing chronic kidney disease (CKD) before discontinuation, and one case developed a new CKD after discontinuation) and one patient underwent transplantation. CONCLUSIONS: The discontinuation of eculizumab in patients with aHUS is not without risk; it can result in HUS recurrence. Eculizumab discontinuation can be performed with close monitoring of the patients. It is essential to assess risk the factors for relapse before eculizumab discontinuation, in particular in children with a positive complement variant and any degree of residual CKD, as HUS relapse may lead to additional loss of kidney function. Resuming eculizumab promptly after relapse is effective in most patients.

Peritoneal Dialysis-Associated Peritonitis Caused by Mycobacterium abscessus in Children-A Case Report.

Peritoneal dialysis (PD)-associated peritonitis constitutes a major complication associated with the procedure. PD-associated peritonitis caused by nontuberculous mycobacteria, usually as a result of an infection related to the PD catheter, has been reported in adults and is associated with significant complications and poor outcome. The management of PD-associated peritonitis caused by Mycobacterium abscessus is particularly challenging because this species is resistant to many antimicrobials commonly used to treat mycobacterial species. We present here the second reported case of PD-associated peritonitis caused by M. abscessus in children. Our patient was a 9-year-old boy with end-stage renal disease (ESRD) who presented with suspected peritonitis, and his PD fluid cultures eventually grew M. abscessus. The patient received a 3-week course of triple therapy with clarithromycin, amikacin, and meropenem in addition to PD catheter removal. The infection completely resolved even though a susceptibility report at the end of treatment revealed that the isolate was resistant to clarithromycin and had decreased susceptibility to carbapenems. Our observations suggest that PD catheter removal is important in PD-associated peritonitis caused by M. abscessus in children and that more studies are needed to define the optimal length of treatment.

Serum retinol, retinol-binding protein, and transthyretin in children receiving dialysis.

OBJECTIVE: We investigated the relationships of retinol (ROH), retinol-binding protein (RBP), and transthyretin (TTR) in children with end-stage renal disease (ESRD). Our hypothesis was that levels of ROH and RBP would be elevated in children with ESRD. METHODS AND PATIENTS: We measured ROH, RBP, and TTR serum concentrations in a group of pediatric ESRD patients biannually. Children were grouped according to age and method of dialysis, i.e., hemodialysis (HD) or peritoneal dialysis (PD): HD1, aged <12 years (n = 8); PD1, aged <12 years (n = 19); HD2, aged >or=12 years (n =19); and PD2, aged >or=12 years (n = 29). RESULTS: No differences in ROH, RBP, TTR, or their ratios were found as a function of type of dialysis in groups PD2 and HD2. The ROH and TTR were significantly higher in PD1 than HD1 (P = .01 and P = .003, respectively). No correlations were evident between ROH and RBP or TTR with length of time on dialysis, serum calcium, or serum creatinine, except for group PD2, in which ROH was positively correlated with RBP (P = .025). There were no significant differences among any of the ratios in terms of age or method of dialysis. CONCLUSIONS: The data indicate that children with ESRD exhibit elevated levels of serum ROH, RBP, and TTR, in proportions similar to those reported in the adult ESRD literature. Further study is needed to clarify the consequences of increased ROH in uremic children.

Two-dose daclizumab induction in pediatric renal transplantation.

DCZ, an IL-2 receptor antagonist, has been widely used for induction therapy in pediatric and adult solid organ transplantation. Originally, it was recommended as a five-dose regimen; however, fewer doses may be efficacious and less costly for prevention of rejection. There is limited experience with the use of fewer doses in pediatric renal transplantation. We retrospectively reviewed the outcomes of 26 primary pediatric renal transplants performed at a single center between June 2004 and May 2007 receiving induction therapy with two-dose DCZ (1.5 mg/kg preoperatively and day seven post-transplant). Maintenance immunosuppression included tacrolimus, MMF, and prednisone in all patients. Forty-six percent were African American and 92% were deceased-donor transplants. After a mean follow-up of 17.8 +/- 7.5 months, acute rejection was noted in 11.5% and graft survival was 92.3%. CMV infection occurred in 11.5%, but no case of BK nephropathy or post-transplant lymphoproliferative disorder was observed. Our preliminary results suggest that induction therapy with two-dose DCZ was convenient, economical, and effective in preventing rejection episodes without an increase in adverse events or hospital stay. Larger randomized clinical trials with longer duration of follow-up are needed to more fully validate the use of this regimen in pediatric renal transplantation.

Ceftriaxone induced hemolysis complicated by acute renal failure.

Over the last decade, second and third generation cephalosporins have been the most common drugs causing hemolytic anemia (HA). Of these cases, 20% have been attributed to ceftriaxone. The clinical presentation of ceftriaxone-induced HA is usually abrupt with sudden onset of pallor, tachypnea, cardio-respiratory arrest and shock. Acute renal failure (ARF) has been reported in 41% of such cases with a high fatality rate. We report a pediatric patient with ARF complicating ceftriaxone-induced HA who survived. Ceftriaxone is a commonly used drug, and early recognition of HA and institution of supportive care, including dialysis is likely to improve the outcome.

Pasteurella multocida urinary tract infection in a pediatric patient with end-stage renal disease.

Pasteurella multocida is a Gram-negative bacillus that is part of the normal oral flora of cats and dogs. Most infections involving P. multocida are soft tissue infections after animal bites or scratches. We present a case of P. multocida urinary tract infection in a 13-year-old boy with end-stage renal disease receiving peritoneal dialysis. He was successfully treated with intravenous ampicillin-sulbactam followed by oral amoxicillin-clavulanate. Thirteen additional cases of P. multocida urinary tract infection (12 adults and one pediatric patient) reported in the literature were reviewed. Underlying medical illnesses and structural urologic abnormalities are risk factors.

Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess.

Cystic fibrosis (CF) and apparent mineralocorticoid excess (AME) syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR) gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11ß-hydroxysteroid dehydrogenase type 2 enzyme (11ßHSD2), which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR) resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11ßHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.

Membranous glomerulonephritis: treatment response and outcome in children.

The aim of this study was to characterize clinical features, treatment response, and outcome of idiopathic membranous glomerulonephritis (MGN) in a single-center cohort of children. A retrospective review of biopsy-proven idiopathic MGN in 12 children (mean age 11.9 years) was undertaken. Presentation was nephrotic syndrome (NS) (75%), hematuria/proteinuria (17%), and asymptomatic proteinuria (8%). Ten patients (83%) with NS and nephrotic range proteinuria (NRP) were treated with prednisone, and two patients with non-NRP were not treated with immunosuppressive medications. Steroid response in the treated patients was complete (10%), partial (40%), and absent (50%), respectively. Oral cyclophosphamide was used in seven patients of whom five were steroid resistant, one was steroid dependent, and one was partially responsive. At the mean follow up of 27 months, outcome parameters included an estimated glomerular filtration rate of 128 cc/min per 1.73 m(2), albumin of 4.2 gm/dL, and a urine protein/creatinine ratio of 0.87 [median 0.16 (range 0.02-6.52)]. Remission was complete in 75% of the patients and partial in 17%. One patient (8%) with chronic kidney disease (stage 2) was unresponsive to therapy. Complete remission was significantly associated with the absence of chronic histological changes (p = 0.03). In conclusion, children with NS and/or NRP associated with MGN appear to have a good prognosis when treated with a combination of corticosteroids and cyclophosphamide.

Treatment of severe edema in children with nephrotic syndrome with diuretics alone--a prospective study.

BACKGROUND AND OBJECTIVE: Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) <1%. VC patients received IV albumin and furosemide. VE patients received IV furosemide and oral spironolactone. On the basis of phase 1 observations, FeNa <0.2% identified VC in 20 phase 2 patients. RESULTS: All phase 1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff of 0.2%; it was noted that VC patients had higher BUN, BUN/creatinine ratio, urine osmolality, and lower FeNa and urine sodium compared with VE patients. Similar results were observed in phase 2. VC patients had significantly higher renin, aldosterone, and antidiuretic hormone levels. In phase 2, 11 VE patients received diuretics alone and 9 VC patients received albumin and furosemide. There was no difference in hospital stay and weight loss in VC and VE groups after treatment. CONCLUSIONS: FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone in VE patients is safe and effective.

Serum osmolal gap in patients with idiopathic nephrotic syndrome and severe edema.

Pseudohyponatremia in idiopathic nephrotic syndrome with severe edema is attributed to hyperlipidemia that results in displacement of a portion of water phase of plasma. Current methods of measurement of serum electrolytes are unaffected by hyperlipidemia. In this report we demonstrate that patients with idiopathic nephrotic syndrome with severe edema and true hyponatremia may have an increased rather than normal osmolal gap. We believe that this could be secondary to non-Na+ and non-K+ osmoles in response to plasma-volume contraction secondary to hypoalbuminemia. This observation has implications for management of severe edema in such patients, because fluid restriction could increase their risk for pre-renal failure.

Intravenous immunoglobulin, HLA allele typing and HLAMatchmaker facilitate successful transplantation in highly sensitized pediatric renal allograft recipients.

The use of intravenous immunoglobulin (IVIG) in sensitized transplant candidates has resulted in reduced HLA antibody levels and shorter transplant wait times. In addition, the HLAMatchmaker program has been used to identify acceptable mismatches to permit transplantation in highly sensitized patients. We used IVIG desensitization in conjunction with high resolution HLA allele typing and HLAMatchmaker grading of donor offers to facilitate successful transplantation in two highly sensitized children who were awaiting second renal transplants. Both patients lost their initial transplant in <10 days to accelerated acute rejection, and were on dialysis for an average of 50 months with high panel reactive antibody (PRA) levels. They were started on monthly IVIG infusions (2 g/kg/dose). Within one wk following their third and fifth IVIG doses, both patients received a crossmatch compatible, deceased donor renal transplant selected by HLAMatchmaker as a suitable donor offer. Both patients remain rejection free with excellent renal function 19 and 15 months post-transplant, respectively. In conclusion, combining IVIG therapy and donor selection by HLA humoral epitope matching permitted successful transplantation of two highly sensitized children. Further studies in larger numbers of patients with longer follow-up are needed to determine the individual role played by, and relative importance of each component of this combined strategy.

Idiopathic collapsing focal segmental glomerulosclerosis in pediatric patients.

The aim of this study was to evaluate the clinical outcome of our patients with idiopathic collapsing focal segmental glomerulosclerosis (FSGS) as compared to those with non-collapsing FSGS. The study included a total of 39 patients with idiopathic FSGS. Of these, 11 had collapsing FSGS and the remaining 28 were collectively grouped as non-collapsing FSGS. The mean ages, gender ratio (M:F), and percentage of African-American patients in collapsing versus non-collapsing FSGS groups were 12.7+/-3.1 and 8.9+/-5.1 years, 1.2:1 and 4.6:1, and 90.9 and 53.6%, respectively. After a mean followup period of 31.5+/-22.3 months, 8 patients (73%) with collapsing FSGS had chronic renal impairment as compared to 8 (29%) patients with non-collapsing FSGS group after a mean follow-up period of 18.7+/-12.9 months. However, the cumulated renal survival at 30 months did not reveal a significant difference. In comparison to non-collapsing FSGS, collapsing FSGS in our study was equally common in females as in males and occurred predominantly in African Americans. The outcome of our patients with collapsing FSGS at 30 months was better than in previous reports.

MR angiography in the evaluation of a renovascular cause of neonatal hypertension.

Neonatal hypertension occurs in 2% of all infants and it is caused by renovascular abnormalities in 70% of these infants. The gold standard for diagnosing renovascular disease is conventional renal angiography. However, in neonates the procedure is not commonly used because of its invasive and technically challenging nature. MRI and MR angiography (MRA) are less invasive yet reliable means of detecting renovascular disease in adults. There is minimal literature on the use of MRI/MRA in neonatal hypertension. We report a neonate with hypertension secondary to a renovascular abnormality in which MRI/MRA was helpful in uncovering segmental renal artery stenosis. The infant underwent partial nephrectomy with subsequent resolution of his hypertension. Further studies are needed to validate the use of MRI/MRA in the evaluation of neonatal hypertension.

Sirolimus rescue for tacrolimus-associated post-transplant autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) has been reported to occur after renal transplantation, and typically does so in the first few weeks post-transplant. We report on a 3-yr-old child who developed cold AIHA nearly 1 yr after an ABO identical, living donor renal transplant from his mother. Numerous transfusions, pulse steroids, repeat plasma exchange treatments, and IVIG were unsuccessful. Nearly 3 wk into his illness, tacrolimus was changed to cyclosporine, and then to sirolimus, and resulted in a prompt response. He currently has a normal renal function and a normal hemoglobin level on sirolimus monotherapy.

Calciphylaxis in pediatric end-stage renal disease.

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patient's clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.

MRI detection of atrophic kidney in a hypertensive child with a single kidney.

The role of magnetic resonance imaging (MRI) in the work-up of secondary causes of pediatric hypertension is typically restricted to that of renovascular causes where main renal artery stenosis is suspected. We report a case of a 10-year-old female child with hypertension, who was thought to have unilateral renal agenesis, because only a solitary left kidney could be visualized on both ultrasound and renal scintigraphy. Our patient underwent magnetic resonance imaging because of suspected renal artery stenosis in her solitary left kidney. At MRI she was found to have a normal left kidney. However, a very tiny, atrophic right kidney was also visualized. A laparoscopic right nephrectomy was performed, which resulted in complete resolution of her hypertension. This case illustrates a possible additional role for MRI in a very small subset of pediatric hypertensive patients: those with a single kidney on ultrasound.

Renal papillary necrosis induced by naproxen.

A 17-year-old healthy girl was admitted to our hospital with diffuse abdominal pain and decreased oral intake of about 11 days duration. About a week prior to admission, she had taken naproxen, 250 mg four times a day for 4 days. Physical examination was normal except for diffuse abdominal tenderness on deep palpation. Investigations revealed high serum BUN (42 mg/dl) and creatinine (4.0 mg/dl). Serum electrolytes and complement (C3, C4) levels and urinalysis were normal. Antinuclear-antibody and anti-dsDNA were negative. Kidney biopsy revealed renal papillary necrosis, acute tubular necrosis, and focal interstitial nephritis. A diagnosis of nonoliguric acute renal failure due to naproxen nephrotoxicity was made. She received intravenous hydration, and oral steroids, which was gradually discontinued in 3 months. A follow-up at 4 months revealed normal renal function with a serum creatinine of 1.1 mg/dl, BUN 7 mg/dl, and normal urinalysis. The report highlights a need for caution while using naproxen or any other nonsteroidal anti-inflammatory drugs, even for a short duration.