FIGURES AND TABLES

Figure 1.

Serum levels of insulin-like growth factor (IGF) system components (means SEM) and putative effects of bone formation in patients with different stages of chronic renal failure (CRF) and end-stage renal failure (ESRF) as compared with healthy controls and patients with primary hyperparathyroidism (pHPT). Serum levels of free IGF-I and IGFBP-1 to -5 were measured by specific immunometric assays. The stages of chronic renal failure (CRF) were defined as follows: CRF I°, mild renal insufficiency with creatinine up to 250 mol/L and hyperparathyroidism but no further clinical signs of chronic renal failure (N = 29); CRF II°, moderate renal insufficiency with serum creatinine levels between 250 and 500 mol/L and additional signs of chronic renal failure such as incipient anemia or metabolic acidosis (N = 48); CRF III°, serum creatinine levels above 500 mol/L plus typical clinical manifestations of the complex uremic syndrome (for example, metabolic acidosis, fluid overload, electrolyte disturbances, accumulation of end-products of protein metabolism, N = 37); ESRF/HD = ESRF patients who were on maintenance renal replacement therapy by hemodialysis (N = 148).

Figure 2.

Immunoblot analysis of insulin-like growth factor binding protein (IGFBP)-4 in sera of CRF patients with different IGFBP-4 levels. Sera from patients with high (1), medium (2), and low (3) IGFBP-4 values were separated by SDS-PAGE, transferred to nitrocellulose, and then immunoblotted with IGFBP-4 antiserum. The molecular weight (kd) of marker proteins is shown on the left. Intact IGFBP-4 () and IGFBP-4 fragments (star) are indicated. Mean IGFBP-4 concentrations (ng/mL; pooled sera of 5 patients in each group), determined by RIA, are 8400 (1), 1840 (2), and 620 (3).

Figure 3.

Relationship between free IGF-I levels and IGFBP-4 (A) or IGFBP-5 (B) in patients with different stages of renal insufficiency [() CRF I°, () CRF II°, () CRF III°, (+ ) ESRF/HD, () ESRF/PD, () RTX]. The stages of chronic renal failure (CRF) were defined as described in the Methods section and in the legend to Figure 1. Free IGF-I and IGFBPs were measured by specific RIA. Normal ranges are indicated. Free IGF-I levels correlated negatively (r = -0.28, P < 0.05) with IGFBP-4 (A) and positively (r = 0.44, P < 0.005) with IGFBP-5 (B).

Figure 4.

Relationship between IGFBP-4 levels and serum creatinine in patients with different stages of renal insufficiency 1 [() CRF I°, () CRF II°, () CRF III°, (+ ) ESRF/HD, () ESRF/PD, () RTX]. The stages of chronic renal failure (CRF) were defined as described in the Methods section and in the legend to Figure 1. IGFBP-4 was measured by specific RIA and showed a positive correlation with serum creatinine (r = 0.58, P < 0.001).

Figure 5.

Relationship between bone histologic findings and IGFBP-4/-5 levels in 28 hemodialysis patients. IGFBP-5 levels correlated positively with cortical bone thickness (A), trabecular bone volume (B), trabecular interconnections (C), and osteoblastic surface (D). In contrast, IGFBP-4 was negatively associated with trabecular thickness (E) and interconnections (F). Transcortical bone biopsies were performed at the iliac crest and histologic parameters were classified as follows: markedly decreased (-2), decreased (-1), normal (0), and increased (1). IGFBPs were measured by specific RIAs.

Table 1 - Clinical data and laboratory findings (reference values in parentheses) in patients with primary hyperparathyroidism (pHPT) and different stages of chronic renal failure (CRF).

Table 2 - Serum levels of IGF-I, free IGF-I, IGF-II and IGFBP-1 to -6 in patients with different stages of chronic renal failure (CRF), end-stage renal failure (ESRF) treated by hemodialysis (HD), peritoneal dialysis (PD) or renal transplantation (RTX) compared to age-matched healthy control subjects (Controls) and patients with primary hyperparathyroidism (pHPT).

Table 3 - Clinical data and IGF system components of HD patients with mixed uremic bone disease with or without histological signs of osteopenia.

Table 4 - Correlations between bone histologic parameters and laboratory findings.