Low Birthweight and Premature Birth Are Risk Factors for Podocytopenia and Focal Segmental Glomerulosclerosis

Abstract

Background: Recent reports suggest that low birthweight (LBW) is a risk factor for kidney diseases, including focal segmental glomerulosclerosis (FSGS), although the underlying pathological mechanism remains unknown. Podocyte loss triggers glomerulosclerosis; however, whether FSGS in LBW children is associated with podocytopenia is unclear. Methods: We reviewed the birthweights and gestational age of all patients who underwent renal biopsies from 1995 to 2011 at our Institute. Sixteen patients had FSGS, of which 6 (37.5%) had LBW; this LBW rate was significantly higher than the overall LBW rate in Japan (9.7%). The incidence of LBW was also high in patients with minimal change nephrotic syndrome (MCNS; 12.5%). The glomerular cell numbers in biopsy sections were calculated using computer image analysis and compared with FSGS of normal birthweight (NBW-FSGS). Biopsy specimens from age-matched patients with MCNS were also compared. Wilms' tumor-1 (WT1) immunohistochemistry was performed to enumerate the podocytes. Results: All patients in the LBW-FSGS group were also preterm, with an average gestational age of 25.8 weeks. The number of podocytes per glomerulus in the LBW-FSGS patients was 34 and 24% lower as compared to that in the MCNS patients (p < 0.01) and the NBW-FSGS patients (p < 0.05), respectively. Similar results were observed for the WT1-positive glomerular cell number. Conclusion: LBW and premature birth were associated with FSGS development. The possibility that LBW and premature birth may be predisposing factors for severe podocytopenia in children with FSGS warrants further investigation.

Proteinuria caused by glomerular hypertension during adolescence associated with extremely premature birth: a report of two cases

“…Their renal pathological findings included glomerulomegaly, hypertrophy of the juxtaglomerular apparatus, and perihilar segmental sclerosis, all consistent with glomerular hypertension [8][9][10]. Lesions of secondary segmental sclerosis caused by hyperfiltration tend to be in the perihilar area [8,10].…”

“…Moreover, the presence of IUGR complicating prematurity increases the risk of CKD owing to impaired glomerulogenesis and podocyte injury [6,7]. A study of six patients with focal segmental glomerulosclerosis with a mean gestational age of 25.8 weeks and weight appropriate for age suggested that glomerular structure prematurity may be a more important factor than podocyte injury during the fetal period [9]. Nephrogenesis in humans begins during the 9th week of gestation, continuing up to week 36, with marked development occurring during the third trimester [17].…”

“…Their individual conditions in utero are not the same, and several studies have reported their long-term renal complications [3][4][5], including those with and without intrauterine growth restriction (IUGR) [6,7] and prematurity [8,9]. Few reports, however, have described their individual clinical background, renal pathological findings, and the efficacy of treatment [8][9][10]. This report describes the pathophysiological assessments of two adolescents, born extremely prematurely (gestational age <28 weeks) and with a birth weight appropriate for gestational age, who developed proteinuria during adolescence.…”

Factors associated with a vicious cycle involving a low nephron number, hypertension and chronic kidney disease

“…Subsequently, numerous animal experiments and epidemiological studies have demonstrated a similar concept, additionally focused on the association between LBW and a low nephron number. 22,23 In addition, Hodgin et al 24 described the onset of secondary focal segmental glomerulosclerosis (FSGS) as being associated with proteinuria in six adults with a history of extreme prematurity, and Ikezumi et al 25 reported the number of podocytes per glomerulus in LBW-FSGS patients is lower than that seen in MCNS patients born with a normal birth weight. These findings support the hypotheses of both Barker and Brenner that LBW is associated with a reduced nephron number and therefore an increased risk of HTN/CVD and CKD in later life.…”

Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

“…It is the leading cause of steroid-resistant nephrotic syndrome and the most common cause of chronic kidney disease among glomerular diseases (Reidy and Kaskel, 2007;D'Agati et al, 2011). The recent epidemiological data, suggesting that IUGR is a risk factor for glomerulosclerosis, was supported by the finding of higher Toxicology and Applied Pharmacology 287 (2015) [128][129][130][131][132][133][134][135][136][137][138] incidence of glomerulosclerosis among the patients who had low birth weight (Hodgin et al, 2009;Ikezumi et al, 2013). Animal studies also demonstrated that some suboptimal intrauterine environments, such as 50% intrauterine food restriction (Regina et al, 2001), could lead to glomerulosclerosis of adult IUGR offspring.…”