Primary focal segmental glomerulosclerosis--long-term outcome after pediatric renal transplantation

Recurrence of the primary disease is a significant issue in pediatric renal transplantation (RTx). According to data reported by the North American Pediatric Renal Transplantation Cooperative Study, patients with focal segmental glomerulosclerosis (FSGS) as primary renal disease have a recurrence rate of 30% after the first RTx. The relative risk of an early graft loss because of recurrent disease is increased to 1.6-3.1 in pediatric patients with FSGS. In a German open multicenter study, which was initiated to investigate mycophenolate mofetil (MMF) after pediatric RTx [Transplantation 2001:71:638, Transplantation 2003:75:454], patients with FSGS were evaluated for recurrence rate, risk factors for recurrence, long-term graft function, glomerular filtration rate and transplant survival. All patients received immunosuppression with MMF, cyclosporine A and prednisone without induction therapy. Renal function and survival data for FSGS patients were compared with the results of patients with other primary renal diseases within the same study population. Among 86 patients transplanted between 1996 and 1999 eight patients suffered from FSGS as primary disease. Recurrence was diagnosed in two of the eight patients. One out of these two patients lost his graft as a result of recurrence. Risk factors such as time between diagnosis and end stage renal disease (ESRD) and age at onset did not predict recurrence. A three-year patient survival in the FSGS group was 100%, graft survival 87% vs. 97% in the non-FSGS group. Acute rejections occurred in three out of eight FSGS patients and in 37 out of 78 among the non-FSGS group. Long-term renal function, calculated using mathematical modeling based on glomerular filtration rate (GFR) data during 3 yr after RTx, was similar in FSGS patients - including a patient who had recurrence with a functioning graft - and those without FSGS. In patients with FSGS, recurring disease after RTx remains an important cause of graft loss (one of two patients in this population) even under modern immunosuppressants. Nevertheless, the immunosuppressive regimen used was associated with a similar graft survival rate and long-term renal function of FSGS patients compared with patients with other primary diseases.     

Short-term effect of low and high protein intake on renal function in children with renal disease

The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51-85 ml/min/1.73 m2 BSA) or severely (9-50 ml/min/1.73 m2 BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3-5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m2 BSA and ERPFs above 150 ml/min/1.73 m2 BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

Short-term protein loading in diabetics with a ten-year duration of disease

The concept of renal functional reserve has recently been introduced. To test this ability of the kidneys to increase the glomerular filtration rate (GFR) above the baseline level, the GFR response to short-term protein load was measured. Recent studies have provided conflicting data concerning the GFR response to a protein load in insulin-dependent diabetics who are known to have increased baseline GFRs. Thus, we studied nine insulin-dependent diabetics with a disease of at least a ten-year duration (none were hypertensive or proteinuric) and compared their data with those of five nondiabetic controls with normal renal function. All the diabetics, except one, showed a significant increase in GFR (mean +/- SEM, 60 +/- 9 to 74 +/- 14 mL/min/sq m); the controls also had increased GFRs (mean +/- SEM, 53 +/- 6 to 69 +/- 6 mL/min/sq m). The one patient who demonstrated no rise in the GFR had the lowest GFR measured, 33 mL/min/sq m. To explore the mechanism of this response, we measured the plasma levels of putative mediators glucagon and human growth hormone. Although glucagon showed the expected rise after the protein meal, the variability was so large that no statistically significant relationship could be identified. Human growth hormone remained constant and low in the controls and showed more variability and was higher in the diabetics; again, no relationship to the GFR could be demonstrated. Thus, our data demonstrated a normal response to a short-term protein load by a group of well-defined diabetic subjects who would be at risk to show subtle renal abnormalities.     

Long-term follow up of renal function in IgA nephropathy.

Fifty one children with IgA nephropathy verified at biopsy have been followed up clinically and functionally for 0.4-16.8 years from the onset of symptoms. Renal function was evaluated by determining the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from the clearances of inulin and para-aminohippuric acid. Fifteen (29%) of the children had raised serum creatinine concentrations at the onset. Mean GFR was significantly lower than that of controls at the first investigation. During the follow up GFR and ERPF decreased and were significantly lower than in the controls after eight years of disease. The significant fall in renal function was found in children with proteinuria and especially in boys, in whom GFR and ERPF decreased from a mean (SEM) of 117 (5) and 616 (31) at 2.8 years to 97 (6) and 509 (36) ml/min/1.73 m2 at 7.5 years. Patients with raised serum creatinine concentrations at the onset had significantly lower GFRs, and patients with macroscopic haematuria at this time did not show decreased renal function at follow up. In conclusion, children with IgA nephropathy do not seem to have a benign clinical course. Boys with proteinuria show a significant decrease in renal function during follow up.     

新生鼠输尿管不全梗阻后肾盂压力和肾脏形态变化的观察

目的 了解新生鼠输尿管不全梗阻后肾盂压力和肾脏形态的变化。方法 65只新生鼠用腰大肌包埋不同长度的左侧输尿管，制成轻（n=31)、重（n=34)度输尿管不全梗阻。对照组仅进行剖腹探查。术后8周和24周分别用核磁共振检查肾脏形态变化，术后分别于24周和30周进行肾盂测压和组织学检查。结果 梗阻肾脏均有不同程度积水。严重梗阻组除积水较严重外，发现4例肾脏肾发育不全，其平均肾实质重量仅是对照组的35％。轻度梗阻组和对照组未见发育不良的肾脏。严重梗阻组的肾脏灌注压明显高于轻度梗阻组和正常对照组。结论 新生鼠输尿管不全梗阻后均产生明显肾积水。严重梗阻组可产生肾脏发育不良，可能与严重梗阻组肾盏灌注压明显增加有关。     

Short-Term Effect of Low and High Protein Intake on Renal Function in Children with Renal Disease

ABSTRACT. The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51–85 ml/min/1.73 m² BSA) or severely (9–50 ml/min/1.73 m² BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3–5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m² BSA and ERPFs above 150 ml/min/1.73 m² BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

Increased fractional excretion of phosphate and beta 2-microglobulin in unilateral renal disease

Following progressive nephron loss tubular reabsorption in the remaining nephrons will fall to preserve solute and electrolyte excretion. We have examined the fractional excretion (FE) of phosphate, sodium, beta 2-microglobulin (beta 2M) and tubular glucose reabsorption (T glucose) in children with unilateral renal disease to find 1) the threshold for this response and 2) whether intrinsic renal mechanisms can elicit this response. Separate renal function studies were performed using unilateral ureteral compression. Total glomerular filtration rate (GFR) was 93.7 +/- 2.99 ml/1.73(m2)-1 X min-1, and 110.25 +/- 5.40 in control children. GFR in the scarred kidney (SK) was 22.4 +/- 2.46 and in the contralateral kidney (CIK) 67.2 +/- 4.60 ml X 1.73 (m2)-1 X min-1. The kidney area was reduced in proportion to GFR in SK. FE phosphate and beta 2M were significantly higher in SK than in CIK (sign test), but absolute values for FE phosphate and beta 2M were not higher in SK than in control kidneys. FE sodium and T glucose were the same in SK and CIK. Conclusion: Following moderate unilateral reduction of GFR selective depression of tubular reabsorption can occur without extrarenal impulses.     

Tubular and glomerular function in children after renal transplantation

Glomerular and tubular function of transplanted kidneys were assessed in 46 children aged 15.7 +/- 4.6 yr, 4.2 +/- 2.8 yr after renal transplantation. There were 34 cadaveric, and 12 living-related donors. Twelve patients (26%) had acute episodes (acute tubular necrosis, rejection, or urinary tract infection) during follow-up. All patients were on triple immunosuppression. The mean serum creatinine was 1.5 +/- 0.6 mg/dL. Creatinine clearance (Ccreat) calculated from a 24-h urine collection was 48.0 +/- 19.7 mL/min/1.73 m(2), and that estimated from the Schwartz formula, 61.0 +/- 22.5 mL/min/1.73 m(2). A positive correlation was found between the calculated and estimated clearances. Mean urine concentrating ability was 487 +/- 184 mOsmol/kg, with a value lower than 400 mOsmol/kg in 35% of patients. There was a positive correlation between urine osmolality and estimated Ccreat. Metabolic acidosis (bicarbonate <22 mmol/L) was found in 41% of patients, with relatively alkaline urine and high chloride level. Fractional excretion (FE) of sodium was above 1% in 68% of patients (mean 1.66 +/- 1.06%), and FE(Mg) was above 3% (mean 10.9 +/- 5.2%) in 93% of patients. Tubular reabsorption of phosphate (TP)/glomerular filtration rate (GFR) was 3.2 +/- 0.8 mg/dL glomerular filtrate (GF). FE(K), FE(UA), and Ca/creatinine in urine were normal. There were no functional group differences between the cadaveric and living-related kidneys. Significant group differences were found in those with acute episodes and those with a normal course. Estimated Ccreat was 54 +/- 20 vs. 67 +/- 20 mL/min/1.73 m(2) in the acute episodes and the normal course groups, respectively. Also, the FE(NA), FE(UA), and FE(Mg) were higher in the acute episodes group -2.3 +/- 1.6, 10.6 +/- 4.4, and 14.8 +/- 6.5%, respectively, compared with the normal course group -1.4 +/- 0.6, 8.2 +/- 2.8, and 9.6 +/- 4.0%, respectively. There were no between-group differences in plasma bicarbonate, FE(K), TP/GFR, and urine osmolality. We believe that most, if not all tubular dysfunctions in the transplanted kidney are secondary to renal failure and interstitial damage from acute episodes and nephrotoxic drugs. These dysfunctions are similar to those in chronic renal failure, where interstitial fibrosis plays a role in kidney function deterioration.     

Renal prostaglandin E2 synthesis and degradation in the developing rat

Postnatal development of glomerular filtration rate (GFR) and renal blood flow is associated with a fall in renal vascular resistance that may be mediated by vasoactive substances. We examined differences in the regulation of one such substance, prostaglandin E2 (PGE2). The present studies examined renal cortical and medullary PGE2 synthesis and degradation in rats aged 20 days (30.7 g), 31 days (101 g), and 120 days (413 g). PGE2 synthesis in cortical microsomes was highest in 20-day-old rats compared to 31- and 120-day-old rats. In contrast, medullary PGE2 synthesis was lowest in 20-day-old rats compared to 31- and 120-day-old rats. Both cortical and medullary PGE2 degradation were highest in 20-day-old rats and decreased with age. Despite demonstrating significant age-dependent differences in cortical and medullary PGE2 synthesis, 11 days of aspirin given between age 20-31 days blocked PGE2 synthesis in cortex and medulla by 60 and 76%, respectively, but GFR was similar to control 31-day-old rats (0.78 +/- 0.04 ml/min/g kidney weight, aspirin-treated, versus 0.85 +/- 0.03 ml/min/g kidney weight, control), suggesting that observed age-dependent differences in renal PGE2 synthesis is not a major determinant of development of GFR. A more important determinant of GFR may be age- related differences in renal cortical prostaglandin turnover.     

先天性肾积水患儿肾脏水通道蛋白表达与肾实质厚度和肾小球滤过率的相关性

目的：探讨先天性肾积水患儿肾脏水通道蛋白AQP1-4 的表达与肾实质厚度和肾小球滤过率（GFR）变化之间的关系。方法：利用Western blot检测AQP1-4蛋白在10例先天性肾积水患儿(年龄62.3±18.3个月)10个肾组织和6例来自肾母细胞瘤手术切除患儿的正常肾脏组织(年龄62.7±17.1个月)中的相对表达量。同时对患侧肾脏肾实质厚度和GFR进行评估。积水肾脏AQP1-4表达与GFR以及肾实质厚度之间进行Pearson相关分析检验。结果：肾积水组AQP1-4蛋白相对表达均明显低于正常组（P＜0.05）。B超测量术前积水侧肾脏肾实质厚度平均为4.59±2.25 mm。99mTc-DTPA 测定积水侧肾脏GFR较对侧肾脏明显下降（40±12 mL/min vs 105±20 mL/min, P＜0.05）。积水组肾脏中AQP1-4蛋白相对表达量与肾实质厚度之间呈正相关,与患侧肾脏GFR之间亦呈正相关。积水侧肾脏肾实质厚度与GFR之间呈正相关。结论：先天性积水患儿肾脏AQP1-4蛋白表达下降,其表达量与肾实质厚度和肾脏GFR的变化呈正相关。     

Glomerular filtration and tubular reabsorption of glucose in insulin-dependent diabetes in children

Although glycosuria is important in the control of diabetes in children, few studies clearly show its significance as compared to glycemia. The aim of the present study was therefore to determine the two parameters that control glucose presence in urine, i.e. glucose glomerular filtration rate (GFR) and tubular reabsorption (JrG). GFR was measured by using a 110 min polyfructosan perfusion in 96 diabetic children and adolescents. The results are as follows: 1) In this population there is a significant correlation (p less than 0.01) between the quantity of glucose in urine and mean glycemia during the test; 2) polyfructosan clearance that reflects GFR in diabetic children without renal complication is 2.11 +/- 0.04 ml/s 1.73 m2, or 126 +/- 2.4 ml/min 1.73 m2 (mean +/- SEM); it is higher than in the reference values already published; 3) JrG is correlated with glucose filtered load (p less than 0.01), GFR (p less than 0.01) and sodium reabsorption (p less than 0.01). The ratio JrG/GFR could be substituted for the classical concept of "renal threshold", as it can be easily measured and may help in interpreting glycosuria in some diabetic children. To conclude, in IDD children, the parameters controlling glycosuria may be studied by a simple method. The clinical value of such renal exploration has still to be determined.     

Renal histological changes in relation to renal function and urinary protein excretion in IgA nephropathy.

Renal function and urinary protein excretion (UPE) were investigated at the time of kidney biopsy in 24 children with IgA nephropathy. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by clearances of inulin and para-aminohippuric acid. For UPE albumin, IgG, beta 2 microglobulin, and creatinine were analysed. Glomerular global/segmental sclerosis and crescents in the biopsy specimens were assessed, and glomerular and tubulointerstitial changes classified on a five degree scale. The patients with tubulointerstitial or mesangial biopsy changes or glomerular sclerosis had significantly lower GFR than those without corresponding lesions. Patients with segmental sclerosis also had higher excretion rates of IgG, which increased with increasing segmental sclerosis. Six patients had GFRs below 2SD of the controls. Within the group of patients with reduced GFR overt albuminuria, a raised excretion rate of IgG, interstitial fibrosis, and advanced mesangial lesions were more frequent. A rising excretion rate of IgG seems to indicate both reduced GFR and increasing segmental glomerulosclerosis and may be a marker of progressive disease.     

Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria

The renal function in a group of diabetic children (n=29;age;4-17 yr; IDDM duration: 1,5-13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167 +/- 32 vs. 124 +/- 18 ml/min/1.73 m2; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 160). Three years later mean GFR was identical (169 +/- 25 ml/min/1.73 m2) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR (r=0.7; p less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 0.01 vs, control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF, Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2 +/- 3.7 and 8.2 +/- 6.6 respectively vs. 8.65 +/- 4 microgram/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symptom of incipiens nephropathy, If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children.     

Glomerular filtration rate in children following renal transplantation

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.     

Evolution of individual renal function in children with unilateral complex renal duplication

OBJECTIVE: To assess the evolution of individual renal function during the maturation process in terms of single kidney glomerular filtration rate (SKGFR) and split function in children with unilateral complex renal duplication. STUDY DESIGN: We retrospectively reviewed the records of 44 children with unilateral complex duplex kidney. All affected kidneys had a poor or nonfunctioning dysplastic moiety, 28 in the upper pole and 16 in the lower pole. At least 2 radioisotopic examinations, including a 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renogram and a plasma clearance of 51Cr-ethylenediaminetetraacetic acid (Cr-51 EDTA), were performed in all children, the first one performed at a median age of 3 months (range 2 to 15 months) and the last one at 24 months (range 12 to 120 months). They allowed a precise estimation of split renal function, overall glomerular filtration rate (GFR), and SKGFR. RESULTS: Mean overall kidney GFR increased significantly between the two measurements from 63 +/- 12.7 mL/minute/1.73 m2 to 95 +/- 21 mL/minute/1.73 m2 (P <.0001). SKGFR of the duplex side similarly increased from 26 +/- 7.7 mL/minute/1.73 m2 to 38 +/- 12.6 mL/minute/1.73 m2 (P <.0001). In terms of split function, the affected kidney had a remarkable stable function between the two measurements, 40% +/- 8.6 and 39% +/- 8.3 (P=.94), respectively. However, cases with the lowest initial split function (<30%) had the lowest initial SKGFR and the worst further evolution. CONCLUSION: In children with unilateral complex renal duplication, we found on the affected side a significant increase of SKGFR because of renal maturation, whereas mean split function remained stable during follow-up.     

Effects of an early weaning on phosphate transport maturation in the rat kidney: influence of the phosphate content of the diet.

The renal phosphate (Pi) transport system matures during the 3rd postnatal wk in the rat by an increase in the carrier affinity for sodium-cotransported phosphate. This study examines the ability of pups to adapt their renal Pi transport to the dietary phosphorus content during this period of carrier affinity maturation, corresponding to the weaning period in the rat. Clearance experiments and brush border membrane studies were performed on 21-d-old rats weaned early on d 16 onto a low phosphate diet (LPD, 0.19 g/100 g), a normal phosphate diet (control, 0.78 g/100 g), or a high phosphate diet (HPD, 1.5 g/100 g). In LPD rats, the Pi fractional excretion (0.3 +/- 0.1%) was lower than in controls (18 +/- 3%, p < 0.001). It remained very low (0.21 +/- 0.05% in LPD rats versus 40.5 +/- 6.3% in controls, p < 0.001) after Pi perfusion (1.5 mumol.min-1.100 g-1) and the reabsorbed Pi per min, corrected for the glomerular filtration rate, was higher than in the two other groups. The calcium fractional excretion (12.6 +/- 1.02%) in the LPD rats was much higher than in the controls (0.42 +/- 0.2%, p < 0.001). In contrast, HPD rats had an elevated Pi fractional excretion (41 +/- 4%, p < 0.001), whereas reabsorbed phosphate per min corrected for the glomerular filtration rate was not increased by a Pi load.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic partial ureteral obstruction in the neonatal guinea pig. II. Pressure gradients affecting glomerular filtration rate

Neonatal guinea pigs with chronic partial ureteral obstruction (CPUO) and contralateral nephrectomy develop hydroureteronephrosis and reduced glomerular filtration rate (GFR) without significant reduction of renal blood flow. To investigate the role of pressure gradients in determination of GFR, micropuncture studies were performed in animals 23 +/- 3 days of age subjected to left ureteral constriction and right nephrectomy within the first 2 days of life and compared to uninephrectomized controls. Resulting ureteral dilatation was variable, with kidney weight and ureteral diameter being proportional to the rise in ureteral pressure (PU). In individual animals with severe CPUO (ureteral diameter greater than or equal to 3 mm), distal tubular transit time was either normal (31-90 s) or prolonged (greater than 120 s). Superficial single nephron GFR (SNGFR) was inversely correlated with PU. Glomerular capillary pressure and afferent arteriolar colloid oncotic pressure were not affected by CPUO while peritubular capillary, proximal and distal intratubular hydrostatic pressure increased as a function of PU. As a result, afferent effective filtration pressure (EFPA) was reduced in severe (10.0 +/- 1.1 mm Hg) compared to mild CPUO (13.4 +/- 0.5 mm Hg), but was not different from controls (11.3 +/- 0.9 mm Hg). For both control and CPUO groups, superficial SNGFR increased by 0.5 nl/min for each mm Hg increase in EFPA but for a given EFPA, SNGFR was 6 nl/min lower in guinea pigs with CPUO. These results indicate that higher EFPA in animals with mild compared to severe CPUO contributes to maintenance of higher SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of Different Protein Intake on Renal Growth in Young Rats

ABSTRACT. We have examined the effect of high protein intake on kidney growth and function in growing rats. The rats were kept on an isocaloric diet containing 12%, 21% and 50% protein, from weaning (16 days) until the time of investigation (18, 20, 24,40 or 80 days). There was no significant difference between the 12% and 21% protein groups in any of the parameters studied. 50% protein increased body weight (BW) and kidney weight (KW). The increase in kidney weight was already evident after 2 days and exeeded the increase in body weight in all age groups. At 24 days renal cortical DNA and the protein/DNA ratio were significantly increased in the 50% protein group. At 40 days the cortical DNA content, but not the protein/DNA ratio, was significantly increased in the 50% group. The glomerular filtration rate (GFR) was studied at 40 days. Total GFR as well as GFR/BW was significantly higher in the 50% group than in the 21% group. In one protocol the diet was discontinued at age 40 days and the rats were studied at age 80 days. In these rats all parameters of renal size and function were the same as in the rats that had had a normal (21%) protein intake from weaning. We conclude that in young rats high protein intake reversibly increases GFR out of proportion to BW and selectively and reversibly stimulates kidney growth by stimulating cell proliferation.     

Influence of different protein intake on renal growth in young rats

We have examined the effect of high protein intake on kidney growth and function in growing rats. The rats were kept on an isocaloric diet containing 12%, 21% and 50% protein, from weaning (16 days) until the time of investigation (18, 20, 24, 40 or 80 days). There was no significant difference between the 12% and 21% protein groups in any of the parameters studied. 50% protein increased body weight (BW) and kidney weight (KW). The increase in kidney weight was already evident after 2 days and exceeded the increase in body weight in all age groups. At 24 days renal cortical DNA and the protein/DNA ratio were significantly increased in the 50% protein group. At 40 days the cortical DNA content, but not the protein/DNA ratio, was significantly increased in the 50% group. The glomerular filtration rate GFR) was studied at 40 days. Total GFR as well as GFR/BW was significantly higher in the 50% group than in the 21% group. In one protocol the diet was discontinued at age 40 days and the rats were studied at age 80 days. In these rats all parameters of renal size and function were the same as in the rats that had had a normal (21%) protein intake from weaning. We conclude that in young rats high protein intake reversibly increases GFR out of proportion to BW and selectively and reversibly stimulates kidney growth by stimulating cell proliferation.     

黄芪对IgA肾病模型大鼠免疫紊乱调节作用的研究

目的 探讨黄芪对IgA肾病(IgAN)模型大鼠免疫紊乱的调节作用.方法 采用口服牛血清白蛋白(BSA)、皮下注射四氯化碳(CCl4)加用尾静脉注射脂多糖(LSP)复合方法,复制IgAN模型大鼠.实验分为3组:正常组、模型组和黄芪治疗组;黄芪治疗组给予黄芪颗粒剂灌胃,正常组及模型组分别灌注等量蒸馏水.检测各组大鼠血尿、蛋白尿及肾脏病理改变,采用免疫组织化学技术检测各组大鼠肾组织中Th2类细胞因子转化生长因子β1(TGF-β1)、白细胞介素5(IL-5)表达情况,ELISA法检测血清中Th1类细胞因子干扰素γ(IFN-γ)和Th2类细胞因子白细胞介素4(IL-4)的水平.结果 ①IgAN模型组大鼠尿红细胞计数高于正常组和黄芪治疗组(P＜0.01);而IgAN模型组大鼠24 h蛋白尿亦高于正常组(P＜0.05)和黄芪治疗组(P＜0.05).②IgAN模型组大鼠肾小球系膜区、肾小管、肾间质病理损害较正常对照组和黄芪治疗组明显加重;模型组大鼠肾小球系膜区IgA免疫荧光较正常组和黄芪治疗组明显增强.③免疫组化结果显示,正常组肾组织有少量TGF-β1和IL-5表达,而IgAN模型组大鼠肾组织中TGF-β1和IL-5表达明显增强,与正常对照组和黄芪治疗组TGF-β1(P＜0.05)和IL-5(P＜0.05)比较差别有统计学意义.④模型组大鼠血清IL-4含量[(33.74±7.52)pg/ml]显著升高,与正常对照组[(2.36±0.85)pg/ml]和黄芪治疗组[(3.24±1.13)pg/ml]比较差别有统计学意义(P＜0.05);而模型组大鼠IFN-γ水平[(18.79±3.80)pg/ml]显著下降,与正常组[(46.53 ±5.56)pg/ml]和黄芪治疗组[(41.28±2.95)pg/ml]比较差别有统计学意义(P＜0.05).结论 黄芪可降低IgAN模型大鼠血尿和24 b蛋白尿水平,减轻肾脏病理变化及IgA在肾小球系膜区的沉积.可能的机制是通过调节IgAN模型大鼠Th1、Th2平衡紊乱,从而改善血清中Th类细胞因子IL-4和IFN-γ的水平,并减少肾组织中Th2类细胞因子TGF-β1和IL-5的表达,来延缓IgAN的发生发展.