Very Low Birth Weight is a Risk Factor for Secondary Focal Segmental Glomerulosclerosis

Abstract

Background and objectives: Low birth weight (LBW), resulting from intrauterine growth retardation (IUGR) or prematurity, is a risk factor for adult hypertension and chronic kidney disease. LBW is associated with reduced nephron endowment and increased glomerular volume; however, the development of secondary focal segmental glomerulosclerosis (FSGS) has not been reported previously.Design T he index case is a 15-yr-old Caucasian male who was found to have mild proteinuria during routine urinary screening. His birth was complicated by prematurity (23 wk gestational age) and a very low birth weight (1.40 kg). He had had numerous perinatal problems associated with prematurity including respiratory complications, intracranial hemorrhage, necrotizing enterocolitis, bowel obstruction, sepsis, and retinopathy of prematurity. There was no history of hematuria, urinary reflux, renal insufficiency, recent fevers, hearing loss, or familial renal disease. He was taking no medications. The patient was followed for several weeks and was found to have persistent, mild proteinuria not associated with exercise or posture (nonorthostatic).Physical examination revealed a height of 172 cm and a weight of 75 kg (body mass index ϭ 25.4 kg/m 2 ), BP of 127/79 mmHg (90th percentile), and no edema. Renal ultrasound revealed normal-appearing kidneys measuring 10.5 cm and 9.6 cm in length. Laboratory examination showed a hematocrit of 50% (normal ϭ 37% to 45%), white blood cell count 7.8 ϫ 10 9 /L (normal ϭ 4.5 to 13.5 ϫ 10 9 /L) with normal differential, platelet count 221 ϫ 10 9 /L (normal 150 to 450 ϫ 10 9 /L), blood urea nitrogen 15 mg/dl (5.8 mmol/L) (normal ϭ 7 to 18 mg/dl [2.5 to 6.4 mmol/L]), creatinine clearance 100 cc/min, serum creatinine 0.9 mg/dl (75.6 mol/L), total serum protein 7.3 g/dl (73 g/L) (normal 6 to 8.2 g/dl [60 to 82 g/L]), and serum albumin 4.4 g/dl (44 g/L) (normal 3.4 to 5.0 g/dl [34 to 50 g/L]). Serum electrolytes, including sodium, potassium, bicarbonate, chloride, and calcium, were normal. The following serologies were negative: anti-nuclear antibody, anti-double-stranded DNA antibody, hepatitis B surface antigen, and hepatitis C antibody. Serum complement levels, including C3 and C4, were within normal range. Urinalysis revealed a specific gravity of 1.030, pH 5, and protein Ͼ 300 mg/dl, with negative glucose, heme and leukocyte esterase. The 24-h urinary protein was 1.34 g. Microscopic examination of the urine revealed zero to five white blood cells per high-power field, no red blood cells, and no hyaline or granular casts. A renal biopsy was performed to determine the cause of persistent subnephrotic proteinuria.Light microscopic examination showed one core of tissue consisting of renal cortex and a small portion of outer medulla. There were 8 glomeruli, none of which were globally sclerotic. The glomeruli appeared hypertrophied but normocellular, with patent capillaries and glomerular basement membranes of normal thickness. No immune-type fuchsinophilic deposits were identified with the trichrome stain. T...

Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

“…Glomerulomegaly was defined as mean glomerular diameter Ͼ1.4 times normal age-matched control, as described previously. 10 FPE was estimated as the percentage of glomerular capillary surface area of patent capillaries exhibiting effacement.…”

“…Multiple causes of secondary FSGS as a result of decreased nephron number have been described, including unilateral renal agenesis, 8 surgical ablation, and low birth weight. 9,10 Patients with normal numbers of nephrons may develop secondary FSGS as a result of morbid obesity, which causes an increased demand for glomerular filtration that parallels increased body mass. 11,12 Secondary forms of FSGS typically have a lower incidence of nephrotic syndrome and a better overall prognosis when compared with primary (idiopathic) FSGS.…”

The Clinical Importance of Nephron Mass

“…Increased susceptibility to hyperfiltration and glomerulosclerosis associates with preterm birth and LBW in a series of six patients with secondary FSGS and glomerulomegaly, a likely consequence of programmed nephron deficits. 131 Several studies described an increased susceptibility to diabetic nephropathy among individuals of LBW or those with short stature. 67,115,132 More rapid progression or relative resistance to therapy was also observed in LBW individuals with IgA nephropathy, membranous nephropathy, minimalchange disease, nephrotic syndrome, and chronic pyelonephritis.…”

Chronic Kidney Disease: A Life Course Health Development Perspective

“…A single case series of six patients with a history of prematurity who developed secondary focal glomerulosclerosis at an average age of 32 years old has been published (Hodgin et al 2009a), providing an example of prematurity's association with CKD later in life. These individuals were all noted to be born prematurely (gestational ages of 22-30 weeks) and at the time of their presentation had nephrotic-range proteinuria, hypoalbuminemia, and lack of edema without any other risk factors for secondary focal glomerulosclerosis, suggesting that the premature infants are at higher risk for developing focal glomerulosclerosis later in life and raising the possibility of closer renal follow-up for such patients.…”