Compensatory Glomerular Hypertrophy Is Not a Cause of Supranormal Renographic Differential Renal Function in Patients with Ureteropelvic Junction Obstruction / 대한비뇨기과학회지

PURPOSE: Increasing clinical importance is being placed on the role of differential renal function (DRF) for the management of congenital ureteropelvic junction obstructions. Supranormal DRF of a hydronephrotic kidney, on a renal scan, is hypothesized to be due to an increase in single nephron filtration or nephron volume. However, the etiology of this paradoxical phenomenon still remains to be elucidated. We studied the histopathological changes of hydronephrotic kidneys with a supranormal DRF. MATERIALS AND METHODS: 35 children with unilateral congenital hydronephrosis and supranormal DRF (>55%), on preoperative renal scans, who had undergone pyeloplasty, were retrospectively evaluated. There were 3 female and 32 male patients. The mean age at the time of the operation was 12.6 months, ranging from 0.1 to 144 months. Needle biopsies, from 3 different sites at the lower pole of the kidney, were performed during surgery. To evaluate the presence of glomerular hypertrophy, the maximal planar area of the glomeruli was measured under light microscopy. Tissue samples were obtained in same manner from kidneys with no history of urinary tract disease on autopsy, and used as controls. The mean glomerular areas of the patient and control groups were plotted according to the patient's age. RESULTS: The mean glomerular area in the patient group was smaller than in the control group, with the exception of 4 patients. According to the logistical regression, the probability of larger renal glomeruli increased with decreasing DRF (p=0.1155). CONCLUSIONS: The glomerular area of a hydronephrotic kidney, with a supranormal renal function on a renal scan, was not significantly larger than the normal controls. Therefore, we believe that the theory of increased nephron volume as a cause of a supranormal DRF can be excluded.

Compensatory Glomerular Hypertrophy Is Not a Cause of Supranormal Renographic Differential Renal Function in Patients with Ureteropelvic Junction Obstruction / 대한비뇨기과학회지

PURPOSE: Increasing clinical importance is being placed on the role of differential renal function (DRF) for the management of congenital ureteropelvic junction obstructions. Supranormal DRF of a hydronephrotic kidney, on a renal scan, is hypothesized to be due to an increase in single nephron filtration or nephron volume. However, the etiology of this paradoxical phenomenon still remains to be elucidated. We studied the histopathological changes of hydronephrotic kidneys with a supranormal DRF. MATERIALS AND METHODS: 35 children with unilateral congenital hydronephrosis and supranormal DRF (>55%), on preoperative renal scans, who had undergone pyeloplasty, were retrospectively evaluated. There were 3 female and 32 male patients. The mean age at the time of the operation was 12.6 months, ranging from 0.1 to 144 months. Needle biopsies, from 3 different sites at the lower pole of the kidney, were performed during surgery. To evaluate the presence of glomerular hypertrophy, the maximal planar area of the glomeruli was measured under light microscopy. Tissue samples were obtained in same manner from kidneys with no history of urinary tract disease on autopsy, and used as controls. The mean glomerular areas of the patient and control groups were plotted according to the patient's age. RESULTS: The mean glomerular area in the patient group was smaller than in the control group, with the exception of 4 patients. According to the logistical regression, the probability of larger renal glomeruli increased with decreasing DRF (p=0.1155). CONCLUSIONS: The glomerular area of a hydronephrotic kidney, with a supranormal renal function on a renal scan, was not significantly larger than the normal controls. Therefore, we believe that the theory of increased nephron volume as a cause of a supranormal DRF can be excluded.

Chronic metabolic acidosis markedly induces proliferation of mesangial cells in rats / 中国病理生理杂志

AIM: To study the effects of chronic metabolic acidosis on glomerulus, mesangial cells and the production of extracellular matrix. METHODS: Chronic metabolic acidosis was induced by addition of 0.28 mol/L NH_4Cl to drinking water for 3, 7, or 14 days in male Wistar rats (n=10). Light microscope combined with computer software (Motic Images Advanced 3.2) was used to determine the effect of chronic acid loading on renal morphologic changes. The expressions of proliferation cell nuclear antigen (PCNA) and p27 in glomeruli were detected by Western blotting or immunohistochemistry. Fibronectin (FN) mRNA was detected by real-time PCR. The proliferation of mesangial cells in vitro was determined by ~3H:-TdR incorporation. The concentration of FN in cultured supernatant was detected by ELISA. RESULTS: On day 1, 3, 7 and 14, the arterial pH and plasma HCO_3~-: in experimental rats were significantly decreased. There was a significantly increased in the kidney weight and the ratio of kidney to body weigh in experimental rats on day 3, 7 and 14. The glomerular area and cell numbers also increased significantly. Immunoblotting demonstrated decreased p27 expression and increased PCNA expression in isolated glomeruli, and the expression of PCNA increased in a time-dependent manner following the time of chronic metabolic acidosis. Immunohistochemistry showed increased positive PCNA expression mainly localized to mesangial cells. The expression of FN mRNA was significantly elevated in experimental rats on day 7 and 14. In vitro, acid loading induced mesangial cell proliferation and synthesis of FN. CONCLUSION: These results suggest that chronic metabolic acidosis induces mesangial cell proliferation, and its mechanism may be associated with the downregulation of cell cycle kinase inhibitor p27.

Structural-Functional Relationships in Renal Amyloidosis

The pathogenetic mechanism of renal dysfunction in renal amyloidosis is poorly understood. To evaluate the morphologic parameters which are correlated with renal function in this disorder, we have examined renal biopsies from 14 patients with renal amyloidosis by morphometry. Of the 14 patients, 8 were male and 6 were female. They were between 41 and 70 years of age. The serum concentration of albumin and creatinine were 2.1+/-0.7 mg/dl and 1.1+/-0.5 mg/dl, respectively. The 24-hour excretion of urinary protein was 7.9+/-5.2 g. Creatinine clearance was 62+/-23 ml/min/1.73m2. The mean glomerular volume (MGV) was (2.2+/-1.3) 10(6) micrometer3. The surface density of peripheral glomerular basement membrane [Sv (PGBM/glom)] was 0.049+/-0.027 (micrometer3/micrometer3). Volume density of mesangium [Vv (mes/glom)] was 0.31+/-0.14 (micrometer3/micrometer3) and volume density of glomerular amyloid deposition [Vv (amyl/glom)] was 0.21+/-0.14 (micrometer3/micrometer3). The volume density of cortical interstitium [Vv (int/cortex)] was 0.14+/-0.09 (micrometer3/micrometer3). The serum creatinine concentration was significantly correlated with Vv (int/cortex) (r=+0.66, p<0.05). MGV was correlated with Vv (mes/glom) (r=+0.75, p<0.01) and Vv (amyl/glom) (r= +0.68, p<0.05) but showed negative correlation with Sv (PGBM/glom) (r=-0.79, p<0.01). Sv (PGBM/glom) showed negative correlation with Vv (mes/glom) (r=-0.77, p<0.01) and with Vv (amyl/glom) (r=-0.87, p<0.01). Positive correlation was observed between Vv (mes/glom) and Vv (amyl/glom) (r=+0.95, p<0.01). These results suggest that the decreased renal function in patients with amyloidosis is related to interstitial fibrosis rather than glomerular lesions. In addition, glomerular hypertrophy in these patients is related to amyloid deposition in the mesangium and peripheral glomerular basement membrane.

Comparison of Glomerular Size between Focal Segmental Glomerulosclerosis and Minimal Lesion in Children

The pathogenetic mechanism of focal segmental glomerulosclerosis (FSGS) is not known. Some authors suggest glomerular hypertrophy may precede the development of FSGS in patients with minimal lesion. It was recently reported that the size of nonsclerotic glomeruli in adults with FSGS is significantly larger than that of cases with minimal lesion. It is not clear whether glomerular hypertrophy observed in adults with FSGS is also seen in children with FSGS. Thus, we have analyzed 37 renal biopsies from children with FSGS by morphometry and the data were compared with 37 renal biopsies from age- and sex-matched patients with minimal lesion. The number of glomeruli submitted for morphometric analysis was 22.6+/-14.2 in cases with FSGS and 30.9+/-11.4 in cases with minimal lesion. Mean glomerular volume (MGV) in FSGS group was significantly larger than that of minimal lesion [(13.1+/-3.9) x10(5) microm3 vs. (10.1+/-1.9) x10(5) microm3, p<0.001]. The relative interstitial volume of renal cortex in patients with FSGS was significantly larger than that of minimal lesion [(0.106+/-0.051) microm3/microm3 vs. (0.029+/-0.012) microm3/microm3, p<0.0001]. In FSGS, the percentage of glomeruli with FSGS was significantly correlated with relative interstitial volume of renal cortex (r=0.79, p<0.0001). As is the case for adult FSGS, MGV of children with FSGS is significantly larger than that of minimal lesion. Thus, the presence of glomerular hypertrophy observed in biopsies with minimal lesion nephropathy seems to be an indication that the coexistent FSGS lesions are undetected due to sampling problems.

Glomerular Hypertrophy in Focal Segmental Glomerulosclerosis

It is not clear whether glomerular hypertrophy is related to the pathogenesis of focal segmental glomerulosclerosis (FSGS). We analyzed renal biopsies from 20 adults with FSGS by morphometry, and the data were compared with those from age- and sex-matched patients with minimal lesion. Mean glomerular volume in the FSGS group was significantly larger than that in the minimal lesion group[(3.4 + 1.1 vs 2.5 0.5)x10(6) micrometer3, P<0.01]. The percentage of glomeruli with global and segmental sclerosis in FSGS group was significantly correlated with the mean glomerular volume (r=+0.66, P<0.001). Relative interstitial volume of renal cortex in the FSGS group was correlated with the serum creatinine concentration(r=+0.5, P<0.05). These results suggest that glomerular hypertrophy observed in our patients with FSGS was related to nephron loss caused by glomerulosclerosis. The interstitial fibrosis may lead to obliteration of postglomerular interstitial capillary network with secondary elevation of glomerular capillary pressure resulting in progressive loss of renal function.