Objective: The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to ...obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years.
Methods: Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients.
Results: Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m
2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were.
Conclusion: With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patient's care is transferred to a physician caring for adults. (J P
EDIATR 1995;127:913-9)
Renal involvement is common in Henoch-Schoenlein purpura (HSP) and, while ureteral obstruction has been described in patients with the disease, it is rare. We report a female with HSP who developed ...bilateral ureteral obstruction from peri-ureteral vasculitis and subsequent ureteral ischemia. Hydronephrosis and typical findings on contrast urography indicated the diagnosis.
We identified an extremely rare condition, isolated complete deficiency of the fourth component of complement, in a child with systemic lupus erythematosus. The genes for C4 are located within the ...major histocompatibility complex (MHC) on the short arm of chromosome 6. The patient expressed only paternal phenotypes for proteins encoded by the MHC (HLA and GLO), yet was 46XX with no detectable 6p deletion. Genomic DNA from patient, parents, and sibling was digested with restriction enzymes, and blots were probed for five chromosome 6 markers. At all loci, maternal and paternal RFLPs could be distinguished, and the patient showed only paternal bands. RFLP analysis of markers from four other chromosomes showed maternal and paternal contribution. The data are consistent with uniparental isodisomy 6 (inheritance of two identical chromosome 6 haplotypes from the father and none from the mother). Direct analysis of genetic material from both parents, as well as detection of multiple protein polymorphisms encoded on chromosome 6, clearly demonstrates this novel mechanism for the expression of a recessive genetic condition.
Continuous arteriovenous hemofiltration is a form of renal replacement therapy whereby small molecular weight solutes and water are removed from the blood via convection, alleviating fluid overload ...and, to a degree, azotemia. It has been used in many adults and several children. However, in patients with multisystem organ dysfunction and acute renal failure, continuous arteriovenous hemofiltration alone may not be sufficient for control of azotemia; intermittent hemodialysis or peritoneal dialysis may be undesirable in such unstable patients. Recently, the technique of continuous arteriovenous hemodiafiltration has been used in many severely ill adults. We have used continuous arteriovenous hemodiafiltration in four patients at Children's Hospital Medical Center. Patient 1 suffered perinatal asphyxia and oliguria while on extracorporeal membrane oxygenation. Patients 2 and 4 both had Burkitt lymphoma and tumor lysis syndrome. Patient 3 had septic shock several months after a bone marrow transplant. All had acute renal failure and contraindications to hemodialysis or peritoneal dialysis. A blood pump was used in three of the four patients, while spontaneous arterial flow was adequate in one. Continuous arteriovenous hemodiafiltration was performed for varying lengths of time, from 11 hours to 7 days. No patient had worsening of cardiovascular status or required increased pressor support during continuous arteriovenous hemodiafiltration. The two survivors (patients 2 and 4) eventually recovered normal renal function. Continuous arteriovenous hemodiafiltration is a safe and effective means of renal replacement therapy in the critically ill child. It may be ideal for control of the metabolic and electrolyte abnormalities of the tumor lysis syndrome.
We and others have shown an association between autoimmune disorders and the major histocompatibility complex extended haplotype HLA-A1,-B8,-SCO1,-DR3. The primary gene or genes within this haplotype ...conferring such susceptibility, however, have not been defined. In this study, we tested the hypothesis that linkage disequilibrium in this haplotype extends through the DP locus, and that DP type may be linked to membranoproliferative glomerulonephritis (MPGN) and systemic lupus erythematosus (SLE). DP and DQ typing was performed by restriction fragment length polymorphism analysis for 43 chromosomes (19 healthy controls, 9 SLE, 15 MPGN) bearing the -A1,-B8,-SCO1,-DR3 extended haplotype. Although all were DQw2, a variety of DP types were identified (DPw1, 0.26; DPw2, 0.09; DPw3, 0.14; DPw4, 0.44). Although DPw1 was represented on extended haplotypes with greater frequency than on 113 non-A1,-B8,-SCO1,-DR3 haplotypes (0.26 vs. 0.03; P < 0.001), there were no significant differences between healthy individuals with this haplotype and those with autoimmune disease. We conclude that the strong linkage disequilibrium of this haplotype breaks down between the DQ and DP loci. Loci important to disease susceptibility, therefore, are more likely to occur telomeric to DP.
Pediatricians frequently have faced one or more of an array of lower urinary tract symptoms without obvious cause. Now, with increasing recognition, many of these diagnostic enigmas have been ...ascribed to idiopathic hypercalciuria. This article reviews this "new" clinical syndrome, attempts to clarify pathophysiology, and selects patients for therapeutic intervention.
Strontium optical lattice clocks at JILA recently demonstrated record-high accuracy and stability. These advances were enabled by an ultrastable laser with fractional frequency stability of 1 × 10-16 ...at 1 second. This laser allows us to study systematic shifts of the 1S 0 to 3P0 clock transition with unprecedented precision. Density-dependent frequency shifts represent an unavoidable perturbation for clocks based on many atoms. Our studies of atomic interactions in an optical lattice clock system uncover the nature of these interactions and reveal important many-body atomic correlation effects in this open quantum system. By extending our measurements to all ten nuclear-spin sublevels of the clock states, we observe the first direct evidence of SU(N) symmetric interactions in alkaline earth(-like) atoms. Using the techniques we developed in these studies, we also demonstrate a novel technique for measuring the frequency noise spectrum of an ultrastable laser. We discuss designs for the future direction of our experiment which will place 87Sr atoms within a high finesse cavity that is resonant on the 1S 0 to 3P1 transition. We will use this system to study collective effects in cavity quantum electrodynamics. Most notably, strong atom-cavity coupling can enhance the spectroscopic sensitivity of our clock by creating spin-squeezed states via quantum non-demolition measurements. As a precursor to future work studying cavity-mediated collective behavior, we use the unique atomic structure of 88Sr to investigate free-space retarded dipolar coupling in an optically thick sample of atoms.
The radioactive radium-225 (\(^{225}\)Ra) atom is a favorable case to search for a permanent electric dipole moment (EDM). Due to its strong nuclear octupole deformation and large atomic mass, ...\(^{225}\)Ra is particularly sensitive to interactions in the nuclear medium that violate both time-reversal symmetry and parity. We have developed a cold-atom technique to study the spin precession of \(^{225}\)Ra atoms held in an optical dipole trap, and demonstrated the principle of this method by completing the first measurement of its atomic EDM, reaching an upper limit of $|$$d\((\)^{225}\(Ra)\)|\( \)<\( \)5.0\!\times\!10^{-22}\( \)e \cdot\(cm (95\)\%$ confidence).
Complete deficiency of the complement C4A isotype is a known genetic risk factor for systemic lupus erythematosus (SLE). The disease phenotype of C4A-deficient patients has never been defined. Among ...200 patients with SLE from five centers, 18 (9%) with C4A deficiency were identified. These individuals were compared to those who were C4A replete with regard to a series of clinical and serologic features. The only significant differences between the two groups were in the presence of renal disease (C4A deficient, 11%; C4A replete, 46%; P < 0.006) and a decrease in the serum concentrations of C3 (C4A deficient, 11%; C4A replete, 35%; P < 0.04). There was also a trend for the C4A-deficient individuals to have milder disease. In light of the tendency for C4A-deficient individuals to have lower serum concentrations of C4, it is important that such patients not be subjected to overly aggressive efforts to "normalize" their C4 levels.
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