Rachel Frank

Increased urinary nitrite excretion in children with minimal change nephrotic syndrome

OBJECTIVE We tested the hypothesis that nitric oxide synthesis by the kidney is increased in children with primary nephrotic syndrome. METHODS We examined the urinary excretion of nitrite, a stable metabolite of nitric oxide, using the Griess reaction, in children with nephrotic syndrome. RESULTS In comparison with healthy children, patients with minimal change nephrotic syndrome had increased urinary nitrite excretion regardless of whether the disease was in relapse or remission (p < 0.025). In contrast, urinary nitrite excretion was similar in control subjects and patients with focal segmental glomerulosclerosis or IgA nephropathy. CONCLUSION These findings indicate that measurement of urinary nitrite excretion may be a useful test to help discriminate between minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome.

Yield of renal arteriography in the evaluation of pediatric hypertension.

Abstract The prevalence of renovascular disease is estimated to be 3%–5% in pediatric patients with hypertension. The utility of non-invasive imaging tests has not been evaluated in children, and renal arteriography remains the diagnostic test of choice. However, there are no established guidelines for the application of this test and information is not available about the likelihood of detecting an abnormality if an arteriogram is performed in children with hypertension. Therefore, we reviewed the yield of renal arteriography in pediatric patients if the test was performed based on the following two criteria: (1) severe hypertension exceeding the 99th percentile for age and sex or (2) failure to control high blood pressure with one antihypertensive drug. During the period 1983–1998, 28 children (mean age 11.7 years) who satisfied one of the above criteria underwent renal arteriography to investigate hypertension. None of the patients were renal transplant recipients. The average duration of hypertension was 11 months and the peak blood pressure was 168/107 mmHg. The renal arteriogram was abnormal in 12 patients (43%). Unilateral renal artery stenosis was the most-common abnormality. When the patients were divided into two groups – those with an abnormal or normal test result – they did not differ in age, sex, or racial distribution. The peak systolic blood pressure was higher in children with an abnormal renal arteriogram (P<0.05). Among those undergoing the arteriogram on the basis of the first criterion, i.e., severe hypertension, 11 of 23 (48%) studies were abnormal. Five children had an arteriogram based on the second criterion – failure to control the blood pressure with one medication – and in 1 patient (20%) the test was abnormal. We conclude that the prevalence of renovascular disease in a population of hypertensive children subjected to renal arteriography is around 40%. Two clinical criteria – namely severe hypertension or failure to control hypertension effectively with one drug – are useful to guide the application of renal arteriography in children with hypertension.

Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome.

BackgroundIdiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.MethodsA retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation.Results13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFRe was 127 ± 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.ConclusionIMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.

Treatment of Recurrent Focal Segmental Glomerulosclerosisin Pediatric Kidney Transplant Recipients: Effect of Rituximab

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is a complication that often leads to graft loss. There is no consensus on the optimal treatment of recurrent FSGS. Rituximab, a monoclonal antibody to CD20, may be a useful treatment of this complication. Methods. We report four pediatric cases of recurrent FSGS treated with rituximab and plasmapheresis. Results. Four children (2M/2F), age 15.3 ± 2.6, with recurrent FSGS posttransplant were identified. Four doses of rituximab were administered 171 ± 180 days posttransplant and 114 ± 169 days after the start of plasmapheresis. Three children responded with complete remission, one of whom relapsed after four months. One child had a partial response with a decrease in proteinuria that was not sustained. No adverse side effects were reported during treatment or followup (mean 22.5 months). Conclusions. Rituximab is a safe and well-tolerated ancillary treatment for recurrent FSGS in pediatric patients in conjunction with plasmapheresis.

Pilot Study of Mycophenolate Mofetil for Treatment of Kidney Disease due to Congenital Urinary Tract Disorders in Children

BACKGROUND Congenital uropathies account for nearly half the chronic kidney disease in children. Immune-mediated injury may contribute to progressive loss of kidney function in affected patients. STUDY DESIGN Open-label uncontrolled pilot study to determine the feasibility of treatment with the immunosuppressive drug mycophenolate mofetil (MMF) to prevent a decrease in kidney function in pediatric patients with congenital uropathies. SETTING & PARTICIPANTS Children treated in an outpatient tertiary-care center were eligible if they had: (1) age of 3 to 16 years, (2) glomerular filtration rate (GFR) less than 50 mL/min/1.73 m(2), and (3) a congenital genitourinary tract abnormality. INTERVENTION After a 2-month run-in period, patients were prescribed MMF, 600 mg/m(2)/dose, twice daily for a 24-month treatment period. OUTCOMES The primary end point was feasibility based on the ability to recruit and retain subjects and lack of unanticipated adverse events. The secondary end point was change in GFR. MEASUREMENTS Patients were monitored by using standard clinical laboratory tests, and GFR was determined by means of iothalamate clearance. RESULTS 12 patients aged 8.9 +/- 4.8 years (10 boys, 2 girls) were treated with MMF for 18.6 +/- 8.0 months; 7 patients completed the entire treatment period. MMF dosage at the final study visit was 381 +/- 241 mg/m(2) twice daily. Gastrointestinal symptoms were the most common adverse effect. There was only 1 serious adverse event, an episode of fever and neutropenia requiring parenteral antibiotic therapy after 21 months of MMF therapy. GFR remained stable throughout the treatment period. Nutritional status, blood pressure, and serum calcium, phosphorus, and cholesterol levels were unchanged during this period. LIMITATIONS Insufficient power to assess the safety or efficacy of MMF therapy for patients with congenital uropathies. CONCLUSION It is feasible to study MMF as an adjunctive therapy to retard the progression of kidney disease in children with congenital uropathies. A multicenter randomized clinical trial is warranted to determine the efficacy of this novel treatment strategy.

Prevention of Serious Bacterial Infections in New-Onset Nephrotic Syndrome: A Survey of Current Practices

are the most serious infections in these patients. The heightened risk of infection is due to abnormalities in circulating immunoglobulin levels, opsonization, cellular immunity, and granulocyte chemotaxis. The secondary effects of treatment with corticosteroids and cytotoxic agents may exacerbate these intrinsic problems.si2 Prophylactic antibiotics and/or pneumococcal vaccines are given to children with nephrotic syndrome in an attempt to prevent infections. However, there are

Is antibiotic prophylaxis indicated for a voiding cystourethrogram

Sirs, Most published data about the association of urinary catheterization and urinary tract infection (UTI) relate to long-term catheterization. In contrast, the risk of UTI from the one-time insertion of a catheter that is subsequently promptly removed appears to be low [1, 2], although at least one sepsis-related fatality is known to have occurred in a 6-week-old male following a voiding cystourethrogram (VCUG) (O. Mehls, personal communication). More recently, in a study of 123 adults who had undergone pressure flow studies, Logadottir et al. [3] reported that 4.1% had a positive urine culture and symptoms of infection 1 week after the procedure, and required antibiotic treatment. The authors concluded that routine antibiotic prophylaxis was not indicated after a study involving a brief catheterization of the bladder. This conclusion was supported by another study of 94 women who had undergone urodynamic testing involving two catheterizations. Those patients were randomly assigned to receive trimethoprim-sulfamethoxazole prophylaxis or a placebo. One week after the urodynamic testing, cleancatch urine samples showed UTI in 5.4% of the treated patients and 6.1% of the placebo patients (P=0.6) [4]. We were able to find only one study of the risk of UTI associated with VCUGs in children. In that retrospective study of 932 children who had undergone VCUGs, 18 patients (1.9%) developed a febrile UTI within 7 days of undergoing a VCUG. The risk was higher in boys, infants, patients with vesicoureteral reflux, and patients with other urinary tract abnormalities, but was not significantly lowered by antibiotic prophylaxis [5]. A few months ago, the occurrence of a UTI a few days after a VCUG in one of our patients prompted us to try to determine whether or not pediatric nephrologists routinely provide antibiotic prophylaxis to their patients who are scheduled to undergo a VCUG. To achieve this, we sent the following email to the subscribers of the PEDNEPH Internet Pediatric Nephrology List: UTI occurs in a small proportion of patients who undergo a VCUG. Do you prescribe prophylactic antibiotic treatment against that risk? Fifty-three responses were received. We included our own answers to the question for a total of 56 responses. Two respondents gave equivocal answers that were not included in the final count. One of those prescribed an antibiotic, after the procedure, only when the catheterization was difficult. The other prescribed prophylaxis for infants but not for older children. Of the remaining 54, 25 (46%) reported that they did not routinely provide prophylaxis and 29 (54%) reported that they did. There was a disparity in the practice of pediatric nephrologists working in the United States and those working in other countries. Of the 35 American respondents, 20 (57%) did not recommend prophylaxis and 15 (43%) did. Of the 19 non-American respondents, only 5 (26%) did not recommend prophylaxis, while 14 (74%) did. The difference between American and non-American nephrologists was statistically significant (chi-squared 4.71, P 0.05). In view of the absence of a clear-cut association between VCUG and post-VCUG UTI, after many years of performing the procedure, we suggest that UTI is an infrequent complication and that antibiotic prophylaxis cannot be considered the “standard of care.” This conclusion is supported by the fact that only slightly more than half of pediatric nephrologists who responded to our question recommended prophylaxis. What little evidence is available does not support antibiotic prophylaxis for VCUGs. B. Gauthier · M. Vergara · R. Frank · S. Vento · H. Trachtman Division of Nephrology, Schneider Children’s Hospital of the North Shore-Long Island Jewish Health System, Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York, USA

URINARY TRACT INFECTIONS, VUR, AND AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

This case series of 16 patients with autosomal dominant polycystic kidney disease (ADPKD) describes 4 girls who presented with a urinary tract infection (UTI). Radiological evaluation revealed that each of these patients had vesicoureteral reflux (VUR). The frequency of VUR was significantly higher in the patients with ADPKD compared with otherwise healthy age-matched children who underwent testing after a UTI (100% versus 15%, P<0.002). These findings suggest VUR is an associated somatic anomaly in children with ADPKD that may contribute to the occurrence of UTI in this patient population.

Role of race in kidney transplant outcomes in children with focal segmental glomerulosclerosis.

It is well established that racial differences exist in kidney transplant outcomes; however, there are no studies which focus on the role of race in transplant outcomes specifically in children diagnosed with FSGS. Associations between race and transplant outcomes in FSGS children were evaluated using the Organ Procurement and Transplantation Network database from 2000 to 2012. Recipients aged 2–21 years who received a kidney‐only transplant were included. Multivariate regression models were used to evaluate transplant outcomes by race. Five hundred and thirty‐six recipients (59.7% male, 15.6±3.9 years) were black and 1134 (55.7% male, 14.3±5.0 years) were non‐black. Graft survival was significantly shorter in the black group (4.2±3.1 vs 4.6±3.3 years, P=.005). Black race was associated with significantly higher risk of graft failure (HR 1.34, 95% CI=1.21–1.49, P<.0001), acute rejection (OR 1.66 95% CI=1.39–1.97, P<.0001), and delayed graft function (OR 1.51, 95% CI=1.33–1.72, P<.001) compared to non‐black race. There were no significant differences in mortality, prolonged hospitalization, or FSGS recurrence between groups. Race is a significant predictor for worse transplant outcomes in children with FSGS.

Blood Pressure Variability in Children With Primary vs Secondary Hypertension

Increased blood pressure variability (BPV) is correlated with adverse cardiovascular (CV) events in adults. However, there has been limited research on its effect in the pediatric population. Additionally, BPV differences between primary and secondary hypertension (HTN) are not known. Children with primary and secondary HTN underwent 24‐hour ambulatory blood pressure monitoring and echocardiography studies. BPV measures of standard deviation (SD), average real variability (ARV), and range were calculated for the 24‐hour, daytime, and nighttime periods. Seventy‐four patients (median age, 13.5 years; 74% boys) were examined, 40 of whom had primary HTN. Body mass index z score and age were independent predictors of systolic ARV (R2=0.14) and SD (R2=0.39). There were no statistically significant differences in overall or wake period BPV measures between secondary or primary HTN groups, but sleep period diastolic SD was significantly greater in the secondary HTN group (9.26±3.8 vs 7.1±2.8, P=.039). On multiple regression analysis, secondary HTN was associated with increased sleep period diastolic SD (P=.025). No metrics of BPV in the overall, wake, and sleep periods were found to be significantly associated with left ventricular hypertrophy (LVH). The results of this study do not show a strong relationship between overall or wake BPV with primary vs secondary HTN, but the association of secondary HTN with sleep period diastolic BPV deserves further exploration. Contrary to expectation, the findings of this study failed to indicate a relationship between BPV and LVH for all patients as well for primary hypertensive and secondary hypertensive patients.