Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium

Background

Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown.

Methods

A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function.

Results

A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible.

Conclusion

Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.     

Tailored use of belatacept in adolescent kidney transplantation

Adolescent transplant recipients are at risk for nonadherence, development of de novo donor‐specific antibody (dnDSA), and allograft loss. Belatacept, a selective T cell costimulatory blocker, is associated with reduced dnDSA, improved renal function, and prolonged allograft survival when compared to calcineurin inhibitor‐based regimens in adults; however, its use in children is scant. Three adolescents were initiated on belatacept between August 2017 and September 2018 at the time of kidney transplantation. Selection criteria included age ≥ 14 and EBV IgG + serostatus. Intraoperative alemtuzumab and methylprednisolone were given as induction therapy. Tailored maintenance therapy included steroid‐free belatacept and sirolimus for two patients. One patient was initially maintained steroid‐free on belatacept and belimumab, an inhibitor of B cell activating factor to treat concurrent systemic lupus erythematous; steroids were added subsequently. Renal function, biopsy‐proven rejection, dnDSA, allograft survival, infection, nonadherence, and proteinuria were monitored. Renal function was 86, 73, 52 mL/min/1.73 m² at 20, 20, and 8 months, respectively. There was 100% adherence to therapy and no development of dnDSA. All patients had treatable infections. One developed steroid‐responsive acute cellular rejection. Belatacept‐based regimens can be tailored for adolescent recipients with good short‐term clinical outcomes.     

Biliary, Pancreatic, and Sphincter of Oddi Electrical and Mechanical Signals Recorded During ERCP

Measurements of biliary tract motility havefocused on radiologic and pressure measurements toquantify biliary motility rather than measurements ofelectrical activity of the biliary tract. We previously reported the recording of biliary electricalsignals during ERCP and now report on the continueddevelopment and validation of a system to measurebiliary tract electrical activity as well as biliarymechanical activity. In 26 patients presenting with avariety of clinical indications, we recordedmeasurements of electrical activity from the common bileduct sphincter (16 patients), pancreatic duct sphincter(eight patients), and/or sphincter of Oddi (eightpatients). Electrical recordings were performed with aspecially modified ERCP catheter, using two circularelectrodes as well as a custom catheter that measured both electrical and mechanical activity.Electrical activity of the biliary tract wassuccessfully recorded in 25 of 26 patients (96%),including the common bile duct sphincter (16 patients,62%), pancreatic duct sphincter (eight patients, 31%) andsphincter of Oddi (eight patients, 31%). Along with theelectrical recordings, common bile duct sphinctermechanical activity was recorded in 12 patients (67%), pancreatic duct sphincter mechanical activityin six patients (33%), and sphincter of Oddi mechanicalactivity in six patients (33%). Frequency analysis ofelectrical signals revealed a mean frequency(cycles/min) of 4.7 ± 0.5 in the common bile ductsphincter, 4.1 ± 0.6 in the pancreatic ductsphincter, and 4.9 ± 0.7 in the sphincter ofOddi. Phasic mechanical frequency in cycles per minutewas recorded at a frequency of 4.8 ± 0.5 in common bileduct sphincter, 4.0 ± 0.6 in pancreatic ductsphincter, and 5.3 ± 0.9 in sphincter of Oddi.Tonic pressure (averaged 12.1 ± 1.5 mm Hg) incommon bile duct sphincter, 12.4 ± 1.4 mm Hg inpancreatic duct sphincter, and 15.0 ± 5.1 mm Hgin sphincter of Oddi. Analysis of wave form propagations(noted as percentage antegrade, retrograde, orindeterminant) revealed 50% antegrade, 23% retrograde, and 27%indeterminant). One patient was recorded on twooccasions via ERCP; the same patient had anintraoperative recording. All three recordings showedsimilarities. We conclude that measurements of biliary,pancreatic, and sphincter of Oddi electrical andmechanical activity are feasible and can be done as partof ERCP. There was good correlation between biliarytract electrical and mechanical events and differentwave form characteristics were noted for different partsof the biliary tree. Further studies are warranted toevaluate the potential usefulness of measurement of biliary tract electrical activity, and toconfirm its correlation with mechanical events in thepancreato-biliary tree.     

Chloroquine resistance of Plasmodium falciparum is associated with severity of disease in Nigerian children

Chloroquine resistance of Plasmodium falciparum in vitro was significantly higher in isolates from patients with severe malaria than those with uncomplicated disease. This association may be due to either progression of uncomplicated to severe disease following chloroquine failure or increased virulence of chloroquine-resistant parasites. The implication of this for antimalarial treatment policy is discussed.     

Plasma and urinary soluble adhesion molecule expression is increased during first documented acute pyelonephritis.

BACKGROUND: The degree of inflammatory reaction and leucocyte trafficking during acute pyelonephritis has been related to the risk of developing renal parenchymal scarring. Adhesion molecules play a central role in leucocyte recruitment during inflammation. AIMS: (1) To determine whether circulating and urinary concentrations of E-selectin and intercellular adhesion molecule 1 (ICAM-1) were abnormal during first documented acute pyelonephritis; (2) to investigate whether circulating or urinary concentrations were predictive for the development of abnormalities on DMSA imaging. METHODS: Plasma and urine samples were collected from 40 children with a first episode of acute pyelonephritis within one week of infection (acute sample) and at six weeks (late sample). Control samples were collected from 21 healthy age matched controls and 18 age matched controls with febrile illness not secondary to urinary tract infection. RESULTS: Plasma and urinary sE-selectin were higher in acute samples (median 176.3 ng/ml and 0.12 ng/mmol respectively) compared with late (97.8 ng/ml and 0.029 ng/mmol) and both control (65.6 ng/ml and 0 ng/mmol) and febrile control (urine 0 ng/mmol) samples. Plasma sICAM-1 was higher in acute samples (428 ng/ml) than controls (365.2 ng/ml), and acute sICAM-1 urine concentrations were higher than febrile control concentrations (3.2 v 0.7 ng/mmol). No correlations were detected between sE-selectin or sICAM-1 and acute or late DMSA scan changes. CONCLUSION: Plasma and urinary sE-selectin and sICAM-1 are significantly increased during acute pyelonephritis, though no correlation exists between the presence of high plasma or urine concentrations and DMSA scan changes, both during acute infection and six weeks post-infection.     

Increased steroid responsiveness of young children with nephrotic syndrome in Nigeria

A previous study on the nephrotic syndrome (NS) in our unit showed that the histological patterns associated with steroid resistance were more common in children over 5 years of age. AIM: The aim of the study was to determine the incidence of steroid-responsiveness amongst nephrotic children 相似文献   

Predictors of outcome in hospitalized patients with severe hyponatremia

Severe hyponatremia is associated with increased morbidity and mortality. Clinicians treating patients with severe hyponatremia are often torn between a desire to promptly raise serum sodium concentration to a "safe range," and at the same time, to avoid excessively rapid correction of hyponatremia. The aim of this study was to assess the prevalence of severe hyponatremia in hospitalized patients, the etiologic factors involved, as well as treatment and outcome of the patients using a retrospective case series. METHODS: Retrospective study of 168 patients with severe hyponatremia (< 115mmol/L) seen at Grady Memorial Hospital, a tertiary teaching hospital, in Atlanta, Georgia, from 1997-2001. The main outcome measures of interest were death during admission or occurrence of neurologic symptoms before, during or after therapy. RESULTS: One hundred sixty-eight patients met the inclusion criteria out of a total of 5994 patients with hyponatremia treated at our hospital over the study period. Eighty-nine patients (52.9%) were symptomatic. The mean absolute serum sodium at 48-hours of therapy was 120.02 +/- 8.31 mmol/L. Respiratory failure and/or hypoxia was present in 28 patients (16.7%); sepsis was documented in 16 patients (9.5%). Mortality rate was high, 34 patients died (20.2%). On multivariate analysis factors with strong association with mortality of patients with severe hyponatremia were hypoxia, presence of neurologic symptoms, slow correction rates and a diagnosis of sepsis. CONCLUSIONS: The mortality associated with severe hyponatremia remains high. Sepsis, respiratory failure and the presence of symptoms predict poor outcome in hospitalized patients with severe hyponatremia. More aggressive therapy with 3% saline may improve outcome in symptomatic patients. Our data suggest that a slow rate of correction in severe hyponatremia is associated with higher mortality than rapid correction, at least in the short-term.