Disseminated histoplasmosis in pediatric kidney transplant recipients-A report of six cases and review of the literature.

BACKGROUND: We report a case series of histoplasmosis in KTx patients in a children's hospital in an endemic area. METHODS: All KTx cases from January 1, 2002, to August 31, 2016, were reviewed to identify those with disseminated histoplasmosis. RESULTS: The attack rate of histoplasmosis among our KTx patients was 6.9 per 100 cases. The median age at the time of diagnosis was 16 years (11-18). Comorbidities included glomerulosclerosis (3), medullary cystic disease (1), and obstructive uropathy (2) and HIV (1). There were 5 deceased and 1 living-related donor transplants, and no patient had a history of rejection prior to histoplasmosis. Median time from transplant to histoplasmosis was 14.8 months (IQR 2.2-38.3) and 33% occurred in the first year after transplant. Urine and/or serum antigens were positive in all patients. They were either treated with amphotericin B and transitioned to an azole or received azole monotherapy. Most (83%) received chronic suppression with itraconazole. No patients died and relapse occurred in 1 patient after repeat transplant. CONCLUSIONS: KTx patients in endemic areas are at risk for disseminated histoplasmosis. Further study is needed to determine which factors portend the need for fungal prophylaxis in this subset of patients.

Glomerular filtration rate equations do not accurately predict vancomycin trough concentrations in pediatric patients.

BACKGROUND: The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. OBJECTIVE: To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. METHODS: This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. RESULTS: A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r (2) = 0.028) and Bedside CKiD equation (r (2) = 0.028). A weak relationship between serum creatinine and troughs was observed (r (2) = 0.132). Limitations include small sample size and retrospective design. CONCLUSIONS: Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications.

Has the incidence of childhood steroid sensitive nephrotic syndrome changed?

Nephrotic syndrome is among the most common types of pediatric kidney disease. However, there are few published data on its incidence and racial patterns. This study examines the incidence and racial patterns of childhood steroid sensitive nephrotic syndrome (SSNS). For the period 1/1/1996 to 12/31/2006, a retrospective chart review was performed of children less than 10 years of age who presented to Le Bonheur Children's Hospital in Memphis, TN with newly diagnosed SSNS. At the time of diagnosis, 38 children were found to reside in Shelby County, TN, with 31 children residing within the Memphis city limits. The annual incidence of SSNS in Shelby County was 2.4 cases/100,000 children. The incidence was higher in males (4.0/100,000) (p = 0.0002), children less than 5 years of age (3.6/100,000) (p = 0.007), and African Americans (3.7/100,000) compared to Caucasians (0.9/100,000) (p = 0.00006). These findings confirm that SSNS is a rare pediatric disease. They also suggest that the incidence of SSNS in Shelby County is comparable to that in prior reports. Our study is one of the first to show that SSNS may be more common in African Americans.

Post-streptococcal acute glomerulonephritis in children: clinical features and pathogenesis.

Post-streptococcal acute glomerulonephritis (PSAGN) is one of the most important and intriguing conditions in the discipline of pediatric nephrology. Although the eventual outcome is excellent in most cases, PSAGN remains an important cause of acute renal failure and hospitalization for children in both developed and underdeveloped areas. The purpose of this review is to describe both the typical and less common clinical features of PSAGN, to outline the changes in the epidemiology of PSAGN over the past 50 years, and to explore studies on the pathogenesis of the condition with an emphasis on the search for the elusive nephritogenic antigen.

Two cases of hematuria with hemoglobin C trait.

Patients with sickle cell disease commonly experience painless hematuria. Hematuria may be found in patients with sickle cell trait, sickle cell anemia, and sickle cell hemoglobin C disease, but it is believed to be uncommon in patients with other hemoglobinopathies, such as hemoglobin C disease and hemoglobin C trait. We report two cases of children with hemoglobin C trait who presented with persistent painless hematuria. Because it is possible that hematuria in a patient with hemoglobin C trait is purely coincidental, all patients with a hemoglobinopathy and hematuria should undergo a complete evaluation so as not to overlook other causes of hematuria.

Induction therapy for pediatric focal proliferative lupus nephritis: cyclophosphamide versus mycophenolate mofetil.

PURPOSE OF THE STUDY: Although cyclophosphamide has been used with success in children, mycophenolate may be a better alternative with less toxicity. The objective of this study is to determine the efficacy of mycophenolate compared with cyclophosphamide as induction therapy in children with class III lupus nephritis. METHODS: We retrospectively studied pediatric patients with class III lupus nephritis from two pediatric centers from January 1991 to December 2005 who were treated either with monthly cyclophosphamide or mycophenolate mofetil for the first 6 months. Thirteen patients were studied, with seven patients in the cyclophosphamide group and six patients in the mycophenolate group. RESULTS: At 6 months, in the cyclophosphamide group, no patient had achieved complete remission, while 57% were in partial remission. In the mycophenolate group, 66% had achieved complete remission, 17% were in partial remission, and 17% were not in remission. DISCUSSION: In a small group of children with class III lupus nephritis, we observed a trend of more patients in the mycophenolate group achieving remission at 6 months. However, the long-term benefit of using mycophenolate as an induction agent is still unclear.

Factors associated with acute renal failure in children with rhabdomyolysis.

Pigment nephropathy accounts for approximately 3% of all cases of acute renal failure (ARF) in children. Studies of risk factors associated with ARF and the need for renal replacement therapy (RRT) in children with rhabdomyolysis-associated pigment nephropathy consist of retrospective case series with variable inclusion criteria. Our objective was to evaluate clinical and laboratory characteristics, etiology, initial fluid therapy, prevalence of ARF and the requirement for RRT in pediatric patients with acute rhabdomyolysis. Twenty-eight patients (19 male) with a mean age of 11.1 +/- 5.6 years were studied. Acute renal failure occurred in 11 patients (39%), seven of whom (64%) required RRT. Features associated with the need for RRT included history of fever, persistent oliguria, admission blood urea nitrogen level, creatinine, Ca(2+), K(+), bicarbonate and aspartate aminotransferase. Most of these factors are related to the level of renal insufficiency and degree of muscle injury. There was no difference in admission and peak creatine kinase (CK) levels between those who did or did not require RRT. However, all who required RRT had a peak CK level > 5000 U/L.

Gastroenteritis caused by Edwardsiella tarda in a pediatric renal transplant recipient.

Edwardsiella tarda, a member of the family Enterobacteriaceae, is a Gram-negative bacillus that is most often pathogenic in aquatic environments. Human infections with Edwardsiella are rare, with most occurring in immunocompromised or immunosuppressed hosts. Reported infections include meningitis, cholecystitis, endocarditis, osteomyelitis, soft tissue infections, bacteremia and septicemia, dysentery, and gastroenteritis. This report describes a case of E. tarda gastroenteritis in a renal transplant patient receiving immunosuppressive therapy. The epidemiology, diagnosis, clinical presentation, and treatment options pertaining to E. tarda infections are examined.

Diagnosis of de novo localized thrombotic microangiopathy by surveillance biopsy.

Thrombotic microangiopathy has been reported in association with calcineurin inhibitors and less frequently with sirolimus in renal transplant patients. The diagnosis of thrombotic microangiopathy is typically made by diagnostic biopsy in the setting of allograft dysfunction. The finding of thrombotic microangiopathy on surveillance biopsy without a significant elevation of baseline serum creatinine is unusual. The optimal treatment of this disorder remains controversial. Treatment strategies have included dose adjustment, drug substitution, plasmapheresis, and intravenous immunoglobulin G. We report a case of de novo thrombotic microangiopathy diagnosed by surveillance biopsy in a patient without hematologic abnormalities or elevated serum creatinine. This patient had resolution of the renal lesion following conversion from tacrolimus to sirolimus-based immunosuppression.

Five years' experience with thymoglobulin induction in a pediatric renal transplant population.

Antibody induction therapy is used in the majority of pediatric patients undergoing renal transplantation. Our center has previously reported short-term outcomes with TMG as induction therapy. We now present our experience over the last five yr. Patients received TMG intra- and post-operatively at a dose of 1.5 mg/kg/day. The dose was decreased to 0.75 mg/kg/day or held dependent on the patient's WBC and platelet counts. Post-transplant immunosuppression also included corticosteroids, MMF, and either TAC or CSA. Patient and graft survival, number of acute rejection episodes, creatinine clearance, incidence and type of infections, and trough levels of calcineurin inhibitor drugs were monitored during the follow-up period. Thirty-four renal transplants were performed in 33 pediatric patients ranging in age from 1.7 to 17.8 yr. Seventeen rejection episodes occurred during the time of follow-up with three patients having more than one episode, but only three episodes occurred within the first year after transplantation. Three patients had graft loss in the first week after transplantation from primary non-function (1) or technical failure/thrombosis (2). Graft losses occurred in seven additional patients during the time of follow-up with the first loss occurring at 17.7 months. Among patients with functional grafts at one wk after transplant, graft survival at one and three yr was 100% and 73% respectively. There were no patient deaths. There were no cases of post-transplant lymphoproliferative disease or other malignancy. One patient had symptomatic CMV disease. TMG is safe and effective as induction therapy in pediatric renal transplant patients. Late graft loss remains a challenge in the pediatric patient population, particularly in adolescents.

Predominance of nocturnal hypertension in pediatric renal allograft recipients.

Hypertension is common in children with end-stage renal disease who have undergone renal transplantation. We performed ambulatory blood pressure monitoring (ABPM) in renal allograft recipients who were on stable maintenance immunosuppressive medications and were more than six months post-transplant. Echocardiographic measurement of left ventricular mass index (LVMI) was obtained at the time of ABPM. Twenty-nine children with a mean age of 14.8 yr (8-18 yr) were evaluated 4.3 yr (0.6-12.8 yr) after deceased donor (n = 13) or living donor (n = 16) transplantation. BP levels were higher during sleep compared with when awake using the 95th percentile to standardize mean BP for each period: mean BP was expressed as a standard deviation score (SDS) for each time period, awake vs. sleep: systolic (s) BP SDS were 0.43 +/- 1.3 vs. 1.29 +/- 1.2 (p < 0.001) and diastolic (d) BP SDS were 0.04 +/- 1.3 vs. 1.34 +/- 1.2 (p < 0.001). Significant differences between awake and sleep BP were also confirmed using the mean BP for each period expressed as a BPI. Hypertension (HTN) during sleep was more common than awake HTN. Based upon BPI, 21% had sHTN when awake compared with 48% during sleep and 7% had dHTN when awake compared with 41% during sleep (p < 0.05). Based upon mean BP load, 38% had sHTN when awake compared with 55% during sleep and 21% demonstrated dHTN when awake compared with 52% during sleep (p < 0.05). Left ventricular mass (LVM) was abnormally increased in six of 17 children (35%); LVM was not correlated with BP. Children prescribed angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) had significantly lower systolic BP compared with those on calcium channel blocking agents (CCB). Mean sSDS was -0.11 +/- 1.1 in those children on ACEi/ARB compared with 1.6 +/- 1.2 in those on CCB (p = 0.02): sSDS during sleep was significantly lower in the ACEi/ARB group compared with CCB (0.70 +/- 1.1 vs. 2.0 +/- 1.1, p = 0.04). Isolated nocturnal HTN is more common than daytime HTN among clinically stable pediatric renal allograft recipients. Detection and treatment of nocturnal HTN in pediatric allograft recipients could potentially affect graft survival.

Severe combined immunodeficiency associated with nephrogenic diabetes insipidus and a deletion in the Xq28 region.

We evaluated a baby boy with severe combined immunodeficiency (SCID) and X-linked nephrogenic diabetes insipidus (NDI). This patient had less than 10% CD3+ T cells, almost all of which were positive for CD4 and CD45RO. Genetic studies demonstrated a 34.4 kb deletion at Xq28 which included AVPR2, the gene responsible for NDI; ARHGAP4, a hematopoietic specific gene encoding a GTPase-activating protein; and a highly conserved segment of DNA between ARHGAP4 and ARD1A, a gene involved in the response to hypoxia. Other patients with NDI, but without immunodeficiency, have had deletions that remove all ARHGAP4 except exon 1; however, no other patients have had deletions of the highly conserved intragenic region between ARHGAP4 and ARD1A. X chromosome inactivation studies, done on sorted cells from the mother and grandmother of the patient, carriers of the deletion, demonstrated exclusive use of the non-mutant X chromosome as the active X in CD4 and CD8 T cells. Surprisingly, NK cells, monocytes and neutrophils from these women demonstrated preferential use of the mutant X chromosome as the active X. These results are consistent with an X-linked form of SCID, due to the loss of regulatory elements that control the response to hypoxia in hematopoietic cells.

Short-term outcomes of severe lupus nephritis in a cohort of predominantly African-American children.

Renal involvement is one of the major determinants of the outcome in patients with systemic lupus erythematosus. Although African-American ethnicity has been suggested to be a poor prognostic factor in severe lupus nephritis in adult patients, information on outcomes of African-American children with this disease is still very limited. We retrospectively studied the patients diagnosed with severe lupus nephritis by renal biopsy at Le Bonheur Children's Medical Center from January 1990 to December 2003. All patients were below the age of 18 years at the time of biopsy. Clinical features assessed included age, gender, race, estimated glomerular filtration rate (GFR), presence of hypertension, gross hematuria, degree of proteinuria, complement 3 and 4 levels, serum albumin, renal histology and dose of oral prednisone. Forty-four patients were studied: 82% were African-American and 89% were female. Mean age at biopsy was 14.2+/-3 years (median 15.0 years; range 4.7 years to 17.0 years). Renal biopsies were assessed according to the WHO classification. Twenty-seven percent, 43%, and 30% were in class III, IV and V, respectively. At presentation, 55% had hypertension and 23% had a history of macroscopic hematuria. The patients had varying degrees of proteinuria, including 18% with nephrotic syndrome. Eighteen percent had moderate renal insufficiency with estimated GFRs less than 50 ml/1.73 m2 body surface area per minute. All the patients were treated with corticosteroids. Sixty-eight percent also received cyclophosphamide and 20% received either mycophenolate mofetil (MMF) or azathioprine (AZA). Two patients developed end stage renal disease and required chronic dialysis within 12 months of biopsy. At the 12-month follow-up visit, 23% of patients had complete remission and 48% had partial remission. The mean estimated GFR had increased from 96.0 ml/1.73 m2 per minute to 124 ml/1.73 m2 per minute (P=0.03). Mean serum creatinine levels decreased from 1.62 mg/dl to 0.91 mg/dl (P=0.03). Complement 3 levels increased from 54.3 mg/dl to 90.3 mg/dl (P<0.01). Mean serum albumin levels also increased from 2.8 mg/dl to 3.6 mg/dl (P<0.01) and urine protein-to-creatinine ratio decreased from 5.8 to 1.0 (P<0.01). The average prednisone dose decreased from 0.96 mg/kg per day to 0.41 mg/kg per day (P=0.64). In our center, with predominantly African-American children, patients with lupus nephritis presented similarly to those in other studies with predominantly Caucasian patients, and short-term renal outcomes were not different.

Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group.

Children with frequently relapsing nephrotic syndrome (FRNS) often develop adverse effects from prednisone. Attempts to induce long-term remission in such patients have had varying levels of success. In this multicenter, prospective, open-label study, 14 centers enrolled 33 patients with FRNS, all of whom were in remission at the time of entry. Six of the patients were steroid dependent. The patients received mycophenolate mofetil (MMF) 600 mg/m(2) twice daily (maximum 1 g twice daily) for 6 mo. A tapering dosage of alternate-day prednisone was given to each patient during the first 16 wk of MMF therapy. Patients were monitored for relapses of NS during and after MMF therapy. Treatment failure was defined as a relapse of NS. The patients had the following features at study entry: Age 6.8 +/- 2.7 yr (range 2 to 15 yr); 56% male, 44% female; and 50% white; 25% black, and 25% other. Estimated GFR at entry was 138 +/- 42 ml/min per 1.73 m(2). Twenty-four (75%) of 32 patients stayed in remission throughout the 6 mo of MMF therapy. The relapse rate in these patients improved from one episode every 2 mo before MMF to one every 14.7 mo after MMF. Eight patients stayed in remission during the post-MMF period, for periods of 18 to 30 mo, whereas 16 relapsed after stopping MMF. Eight (25%) of 32 patients relapsed while taking MMF. It is concluded that MMF is effective for maintaining remission in patients who have FRNS and receive treatment for at least 6 mo and is associated with a low incidence of adverse events.

Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients.

No data are currently available that describe the clinical outcomes associated with Thymoglobulin (rabbit polyclonal anti-thymocyte globulin) induction in pediatric renal transplant recipients. We report the outcomes of 17 pediatric renal transplant recipients (mean age 10.1+/-5.2 years) transplanted between 1 August 1999 and 31 July 2001. Eleven patients (65%) were Caucasian and 6 (35%) were African-American. Eleven (65%) recipients received cadaveric allografts. Two patients (12%) were second allograft recipients. One patient had primary allograft non-function secondary to vascular thrombosis. Two patients (12%) had delayed allograft function. Immunosuppression consisted of Thymoglobulin induction (mean number of doses 6+/-1.7) with tacrolimus (62%) or cyclosporine A (38%), mycophenolate mofetil, and prednisone. One year post transplant, patient and graft survival was 100% and 93%, respectively. No acute rejection episodes occurred during the first 6 months after transplantation in any of the recipients. Additionally, no rejection episode occurred among the 14 patients followed for 1 year after transplant. The incidences of asymptomatic cytomegalovirus (CMV) and Epstein-Barr virus (EBV) seroconversion at 1 year in seronegative recipients with a seropositive donor were 100% of 4 patients and 0% of 4 patients, respectively. No symptomatic CMV or EBV infections and no post-transplant lymphoproliferative disease have occurred in any patient. These short-term data suggest that Thymogobulin induction is safe and effective in combination with triple immunosuppressive therapy for preventing early rejection in pediatric renal transplant recipients.

Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy.

Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.