The disease typically manifests with abrupt development of the nephrotic syndrome in an otherwise healthy child. There is no hypertension, and renal function is preserved in most of these patients. The protein loss usually is confined to smaller plasma proteins, chiefly albumin (selective proteinuria). The prognosis for children with this disorder is favorable. More than 90% of children respond to a short course of corticosteroid therapy; however, proteinuria recurs in more than two-thirds of the initial responders, some of whom become steroid-dependent with proteinuria recurring when steroids are withdrawn. Less than 5% develop chronic kidney disease after 25 years, and it is likely that most individuals in this subgroup had nephrotic syndrome caused by focal segmental glomerulosclerosis http://ebooksmedicine.net
Table 14.2 Summary of Major Primary Glomerular Diseases
GBM, Glomerularbasementmembrane;IgA, immunoglobulinA;IgG, immunoglobulinG;IgM, immunoglobulinM.
not detected by biopsy. Because of its responsiveness to therapy in children, minimal-change disease must be differentiated from other causes of the nephrotic syndrome in nonresponders. Adults with this disease also respond to steroid therapy, but the response is slower and relapses are more common.
Focal segmental glomerulosclerosis (FSGS) is characterized by sclerosis of some (but not all) glomeruli that involves only a part of each affected glomerulus. FSGS may be primary (idiopathic) or secondary to one of the following conditions:
HIV infection (HIV nephropathy). FSGS is seen in 5–10% of patients infected with HIV, but the incidence is decreasing with improved antiviral therapy.
Secondary to other forms of GN (e.g., IgA nephropathy)
As a maladaptation to nephron loss (as discussed earlier) • Inherited forms, including autosomal dominant forms associated with mutations in cytoskeletal proteins and podocin, both of which are required for the integrity of podocytes.
Primary FSGS accounts for approximately 20% to 30% of all cases of the nephrotic syndrome. It is an increasingly common cause of nephrotic syndrome in adults and remains a frequent cause in children.
Injury to podocytes is thought to represent the initiating event of primary FSGS. However, what causes this injury remains unknown. Some investigators have suggested that FSGS and minimal-change disease are part of a continuum and that minimal-change disease may transform into FSGS, but others believe them to be distinct clinicopathologic entities from the outset. As with minimal-change disease, permeability-increasing factors produced http://ebooksmedicine.net
Table 14.3 Causes of Nephrotic Syndrome
Ingestionofdrugs(gold,penicillamine,“streetheroin”)
Infections(malaria,syphilis,hepatitisB,HIV)
Malignancy(carcinoma,melanoma)
Miscellaneous(beestingallergy,hereditarynephritis)
HIV, Humanimmunodeficiencyvirus.*Approximateprevalenceofprimarydiseaseis95%ofthecasesinchildrenand60%inadults.Approximateprevalenceofsystemicdiseaseis5%ofthecasesinchildrenand40%inadults.
by lymphocytes are suspected but remain unproven. The deposition of hyaline in the glomeruli is caused by the entrapment of plasma proteins and lipids in foci of injury where sclerosis develops. The recurrence of proteinuria in patients underoing renal transplantion for FSGS, sometimes within 24 hours of transplantation, supports the idea that a circulating mediator leads to podocyte damage in some cases.