Obesity-Related Nephropathy in Children

Carolyn L. Abitbol; Maria M. Rodríguez

Disclosures

Pediatr Health. 2009;3(2):141-153. 

In This Article

Historical Perspective: Oligomeganephronia and Secondary Focal Segmental Glomerulosclerosis

In the early 1960s, the French group from Enfants Malades/Necker Hospitals in Paris, France, first described a distinct entity in children that they termed 'oligomeganephronia', which included renal hypoplasia and slowly progressive renal insufficiency associated with enlarged glomeruli by histopathology in the absence of dysplastic elements.[47,48,49] They speculated that the lesion resembled the lesion that was induced by experimental reduction in nephron mass and was the result of a congenital decrease in glomerular number with compensatory hypertrophy of the remaining functioning units.[47,48,49] This appears to be the first reference to the clinical correlation of low nephron mass with compensatory hyperfiltration and subsequent glomerulomegaly and secondary glomerulosclerosis (Figure 1).

In 1974, Weisinger et al. described four adult patients with morbid obesity and associated nephrotic range proteinuria.[50] Shortly thereafter, Cohen described the renal pathology in autopsy specimens from five obese patients with ORG ranging from 3 to 30 years of age.[51] Three of those patients had Prader-Willi syndrome, which is now recognized as a lack of imprinting epigenetic disease affecting a paternal deletion of chromosome 15p11-13.[29] However, the common thread was the presence of obesity and a presumed relative decrease in nephron mass with the pathologic picture similar to that of 'oligomeganephronia' or secondary focal glomerular sclerosis.

Some time later, D'Agati recognized the unique pathologic lesion associated with obesity-related secondary FSGS and subsequently reported the largest series of adults in the emerging epidemic.[5,52] Soon afterward, ORG was described in morbidly obese adolescents with renal biopsies displaying FSGS.[32] Athletes with excessive body size and increased BMI owing to tall stature and large muscle mass have also developed kidney disease with secondary FSGS and glomerulomegaly.[53] This emphasizes the burden of increased body mass on a relative nephron deficit in some vulnerable individuals.

The concept of the additive risks of obesity and low nephron mass in humans gained recognition in the clinical observations of Praga et al.[54] They reported a large series of adults who, after unilateral nephrectomy and in association with obesity, developed proteinuria and progressive kidney failure.[54] The onset of the proteinuria and renal insufficiency was over a prolonged period, usually greater than 10 years, and was characterized by few symptoms despite heavy proteinuria.[54,55] This was considered to be similar to 'hyperfiltration nephropathy', another term for ORG.

Alongside the other studies, this study continues to raise the issue of the long-term prognosis of individuals who undergo unilateral nephrectomy or are born with single kidneys.[56,57,58,59] Although absolute associations remain poorly defined, several long-term retrospective studies found that individuals born with renal agenesis or who were children at the time of nephrectomy appeared to be more prone to developing chronic kidney disease.[56,57,58,59] Clearly, long-term surveillance is very much indicated, particularly in the current environment of the global obesity epidemic.

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