Glomerular Capillary Length Research Articles

Renal morphology and glomerular capillarisation in young adult sheep born moderately preterm.

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman's spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman's space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.

A practical guide to the stereological assessment of glomerular number, size, and cellular composition.

The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity.

SUN-132 PRETERM BIRTH: LONG-TERM EFFECTS ON RENAL MORPHOLOGY AND GLOMERULAR CAPILLARISATION IN ADULT SHEEP

Preterm birth (delivery < 37 weeks of gestation) is an important risk factor for the later development of hypertension and chronic kidney disease. The exact cause of this association is unknown, but likely relates to impaired kidney development in early life. We have previously shown that preterm birth can result in the formation of glomeruli with shrunken capillary tufts in the kidneys of human preterm neonates. We have also shown, in lambs, that preterm birth and/or postnatal mechanical ventilation lead to substantial reductions in glomerular capillary length and filtration surface area at 3 days after birth. If this persists, it has the potential to cause glomerulosclerosis and renal dysfunction. Therefore, in this study we aimed to determine the long-term impact of preterm birth on glomerular morphology in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation or at term (146 days of gestation). The ewes assigned to deliver preterm were administered 11.4mg betamethasone at 48 and 24 hours prior to birth, and the preterm sheep did not require mechanical ventilation postnatally. After weaning, the Preterm (n=6) and Term (n=6) sheep were maintained in natural grass paddocks and were euthanised at 14.5 months of age (early adulthood). The right kidney from each sheep was perfusion-fixed, and stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area in the outer, mid, and inner regions of the renal cortex. Glomerulosclerosis, and interstitial collagen levels in the medulla and cortex, were assessed histologically. Sheep born preterm were on average 2.5 kg lighter at birth than those born at term (p=0.0001), but at 14.5 months of age there was no difference between the Term and Preterm sheep in body or kidney weight (Term: 128 ± 8 g, Preterm: 121 ± 5 g, p=0.45). Renal corpuscle volume was significantly (p=0.03) larger in the Preterm sheep than the Term sheep (e.g. mean for inner cortex – Term: 0.0018 ± 0.0001 mm3, Preterm: 0.0024 ± 0.0003 mm3) with the Preterm sheep exhibiting enlarged Bowman’s spaces; however, there was no difference in glomerular volume between groups. Similarly, preterm birth did not impact mean glomerular capillary length or surface area per glomerulus in adult sheep. There was also no difference between groups in interstitial collagen levels, or glomerulosclerosis index. Although there is some evidence of morphological changes in the kidneys following preterm birth, findings suggest that moderate preterm birth per se does not adversely affect total renal filtration surface area or result in renal disease in early adulthood. It is now important to determine whether glomerular capillarisation is similarly normalised in preterm-born adults that were exposed to mechanical ventilation in the neonatal period.

Effects of preterm birth and ventilation on glomerular capillary growth in the neonatal lamb kidney.

Preterm birth is linked to the development of hypertension later in life. This may relate to impaired glomerular capillary growth following preterm birth. The aim of this study was to determine the effects of preterm birth, and/or ventilation, on glomerular capillary growth in the neonatal lamb kidney. Four experimental groups were analysed: preterm lambs delivered at 130 days gestation (term = 147 days) and mechanically ventilated for 3 days (preterm ventilated: n = 9), 133 days gestational controls (gestational control: n = 5), term controls, unassisted breathing for 3 days (term control: n = 8), and term lambs ventilated for 3 days (term ventilated: n = 5). In perfusion-fixed kidneys, total nephron number, average total capillary length, and surface area per renal corpuscle were stereologically assessed, and total renal filtration surface area (TRFSA) was calculated. In comparison with term controls, preterm lambs had significantly reduced glomerular capillary length, surface area, and TRFSA, indicative of a low renal functional capacity. Term-ventilated lambs exhibited significantly reduced glomerular capillary length and surface area compared with term controls, indicating that ventilation impairs glomerular capillary growth independently of preterm birth. Impaired glomerular capillary growth and subsequent reduced TRFSA following preterm birth may mediate the increased predisposition to hypertension later in life.

Glomerular surface area is normalized in mice born with a nephron deficit: no role for AT1receptors

We examined whether deficits in glomerular capillary surface area associated with a congenital nephron deficit could be corrected by glomerular hypertrophy. Using unbiased stereological techniques, we examined the time course and mode of glomerular hypertrophy in mice lacking one allele for glial cell line-derived neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with approximately 30% less nephrons than wild-type (WT) littermates. An additional group of GDNF Het mice received the angiotensin type 1 (AT1)-receptor antagonist candesartan (Cand; 10 mg x kg(-1) x day(-1)) from 5 wk of age to determine the role of AT1 receptors in the compensatory hypertrophy. At 10 wk of age, the total volume of renal corpuscles, glomerular capillary surface area, and length of glomerular capillaries in the kidneys of GDNF Het mice were all markedly (approximately 45%) less than that of WT mice (P < 0.001). However, by 30 wk, and persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP) did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het-Cand mice was 20-30 mmHg less than that of GDNF Het-vehicle mice at all three ages, but Cand treatment did not significantly alter glomerular capillary dimensions. In conclusion, we have demonstrated that the deficit in glomerular capillary surface area associated with a congenital nephron deficit can be corrected for in adulthood by an increase in the total length of glomerular capillaries. This process does not require AT1 receptor activation.

Low molecular weight heparin in the treatment of puromycin-induced nephrosis

Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH – 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls ( C) n = 7 , LMWH-treated group, n = 9 , subcutaneously (SC), 6 mg/kg every day. The PAN group ( n = 7 ) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC – 2 mg/100 g), and a group PAN+LMWH ( n = 6 ). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density ( L Vcap) and glomerular capillary surface density ( S Vcap) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.

Nephron endowment and filtration surface area in the kidney after growth restriction of fetal sheep.

Low birth weight is associated with adult-onset diseases including hypertension and renal disease; altered renal development after intrauterine growth restriction (IUGR) may underlie such prenatal programming. Our aim was to investigate nephron endowment and renal filtration surface area in fetal sheep in which IUGR resulted from late gestational umbilico-placental embolization (UPE) or natural twinning. UPE was performed between 120 and 140 d of gestation (term approximately 147 d). At autopsy (140 d), body weights of UPE and twin fetuses were, respectively, 34% and 28% lower than controls. Kidneys were sampled using a smooth fractionator approach and glomerular number was estimated using a physical disector/fractionator technique. Glomerular capillary length and filtration surface area were estimated using unbiased stereological techniques. Although relative kidney weights (grams per kilogram body weight) were not different between groups, nephron endowment was 40% lower in twin fetuses compared with controls (34.3 +/- 10.6 x 10(4) and 55.9 +/- 19.8 x 10(4), respectively; p < 0.05); UPE did not alter nephron number (50.7 +/- 13.2 x 10(4)). There was no difference in the glomerular capillary length or surface area between the UPE and control fetuses. IUGR due to twinning leads to reduced nephron endowment whereas late gestational IUGR does not, suggesting that reduced nephron endowment is dependent on the timing of the growth restriction. Our findings demonstrate that reduced birth weight per se does not necessarily imply reduced nephron endowment.

Renal Damage in the SHR/N-cp Type 2 Diabetes Model: Comparison of an Angiotensin-Converting Enzyme Inhibitor and Endothelin Receptor Blocker

The pathomechanisms that cause renal damage in diabetes have not been completely clarified. Treatment with angiotensin-converting enzyme inhibitors (ACE-i) is highly effective but fails to completely prevent end-stage renal disease. The effects of ETA-receptor blockers (ETA-RB) on renal damage are controversial and have rarely been investigated in type 2 diabetes. We compared the influence of the selective ETA-RB LU135252 and the ACE-i Trandolapril on renal structure in the SHR/N-cp rat model of type 2 diabetes. Three-month-old male SHR/N-cp rats were left untreated or received daily either Trandolapril or LU135252. The experiment was terminated after 6 months. The glomerulosclerosis index; tubulointerstitial damage index; and glomerular geometry, glomerular cell number, and capillary density were investigated. Proliferating cell nuclear antigen and desmin expression of podocytes, renal mRNA expression of endothelin (ET-1) and transforming growth factor-β, blood pressure, and urine albumin excretion were measured. The glomerulosclerosis index was significantly higher in untreated diabetic animals than in the groups that were treated with ACE-i and ETA-RB. There were analogous changes in tubulointerstitial damage index. Treatment with either substance comparably lowered urinary albumin excretion in diabetic SHR/N-cp. Podocyte and endothelial cell numbers per glomerulus decreased in untreated diabetic animals; this was prevented by the ACE-i but not by the ETA-RB. Glomerular capillary length density was lower in SHR/N-cp, and this was normalized by ACE-i only. Increased expression of desmin and proliferating cell nuclear antigen expression of podocytes in the SHR/N-cp was abrogated by ACE-i but not by ETA-RB. Treatment with ACE-i or ETA-receptor antagonist resulted in less structural and functional alterations, but the ETA-RB was inferior to the ACE-i. This is particularly the case for podocyte changes pointing to angiotensin II–dependent pathomechanisms.

Glomerular and renal vascular structural changes in alpha8 integrin-deficient mice.

Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the alpha8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. alpha8-deficient (alpha8-/-) mice demonstrate reductions in renal mass, which can range from complete renal agenesis to the development of kidneys that are only slightly smaller than wild-type kidneys. No histologic abnormalities of these kidneys have been described. However, considering the prominent expression of alpha8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of alpha8-/- mice would be completely normal. Therefore, the renal phenotype of adult alpha8-/- mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. alpha8-/- mice displayed a significant reduction in nephron number and an increase in glomerular volume, compared with wild-type control animals. Albuminuria was not different in wild-type and alpha8-/- mice. Quantitative morphologic analyses revealed that the glomeruli of alpha8-/- mice were hypercellular, with an increased number of mesangial cells, compared with wild-type mice. Mesangial matrix deposition (as demonstrated for collagen IV and the alpha8 ligand fibronectin) was expanded in alpha8-/- mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of alpha8-/- mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor alpha2 integrin in alpha8-/- mice. The glomerular capillary length density was significantly greater in alpha8-/- mice than in wild-type mice. Cortical arterial vessel walls were not altered in alpha8-/- mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of alpha8, glomerular and renal vascular alterations in alpha8-/- mice were relatively mild. Only aged alpha8-/- mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of alpha8 can be largely compensated for, at least in younger alpha8-/- mice. It is not yet clear whether the occurrence of collagens that are not normally present in glomeruli and the increased abundance of the collagen receptor alpha2 contribute to maintaining the glomerular structure in alpha8-/- mice. The compensatory mechanisms involved will be the subject of future research.

Effect of angiotensin-converting enzyme inhibition on renal filtration surface area in hypertensive rats

Angiotensin-converting enzyme (ACE) inhibitor treatment leads to protective effects on the cellular structure of the glomerulus and the kidney. The aim of this study was to determine whether ACE inhibition increases renal filtration surface area in the spontaneously hypertensive rat (SHR). SHR were treated with the ACE inhibitor perindopril at a high dose (3 mg/kg/day) or a low dose (0.1 mg/kg/day) during the period of hypertension development, from 7 to 14 weeks of age. Some animals were treated concomitantly with the bradykinin B2 receptor antagonist, S16118. Tail-cuff systolic blood pressure and body weights were measured twice weekly. At termination of treatment, glomerular number and volume, length, and surface area of glomerular capillaries and renal filtration surface area were estimated using unbiased stereological techniques. There were significant dose-related reductions in blood pressure with high- and low-dose perindopril treatment. Neither low- nor high-dose perindopril treatment had any effect on glomerular number or size or glomerular capillary length and surface area. Hence, there was no significant difference in total renal filtration surface area between any of the experimental groups (8721 +/- 610 mm2 in untreated SHR and 7879 +/- 338 mm2 and 8767 +/- 437 mm2 in the low and high dose perindopril-treated groups, respectively). Coadministration of the bradykinin antagonist did not affect any of the glomerular parameters. ACE inhibition during the period of hypertension development does not lead to an enhanced glomerular capillary growth or increases in total renal filtration surface area in this model.

Glomerulosclerosis and progression: Effect of subantihypertensive doses of α and βblockers

Uremia is characterized by inadequately increased sympathetic activity. Sympathetic overactivity is involved in the genesis of hypertension in uremia, but its potential role on progression has not been well investigated. To address this issue, the effect of subantihypertensive doses of an alpha blocker and a beta blocker, and their combination on renal morphology and on albuminuria were investigated in the model of the subtotally nephrectomized rat. Male Sprague-Dawley rats were subjected to surgical ablation (SNX) or sham operation (sham). Three days after surgery groups were treated either with phenoxybenzamine (PBZ, 5 mg/kg body weight/day), metoprolol (MET, 150 mg/kg body weight/day) or their combination (PBZ 2.5 mg/kg body weight/day + MET, 50 mg/kg body weight/day). Renal morphology was evaluated after 12 weeks by quantitative histology, immunohistochemistry, and electron microscopy. Urine albumin excretion and kidney endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) mRNA expression were assessed. Systolic blood pressure was significantly higher in all SNX groups compared with sham-operated controls with no difference in the SNX groups. The number of glomeruli per left kidney was reduced from 30,904 +/- 3212 to 17,480 +/- 2341 by SNX (-43.5%). Mean glomerular volume increased from 2.63 +/- 0.7 in untreated sham operated to 4.11 +/- 0.48 microm 3 x 10(6) in untreated SNX (56.3%). The glomerulosclerosis index did not change in SNX + PBZ rats, but was significantly lower in SNX + MET (0.56 +/- 0.14) and particularly SNX + PBZ + MET rats (0.49 +/- 0.11) than in untreated SNX (0.74 +/- 0.24). Glomerular capillary length density (LV) as a sensitive index of capillary obliteration was significantly lower in SNX and almost normalized in the three intervention groups. The same was true for the mean podocyte number per glomerulus. Glomerular ultrastructure in SNX was largely preserved by all treatments. The albumin excretion rate was significantly higher in untreated SNX than in sham; it was significantly lower in all treated SNX groups. The beneficial effect of non-hypotensive doses of alpha and beta blockers and their combination on renal morphology and albuminuria in the model of renal ablation argue for a blood pressure-independent role of sympathetic overactivity in the genesis of progression. In addition, the beneficial effect of adrenergic receptor blockade indicates that a substantial part is not mediated by sympathetic cotransmitters such as adenosine 5'-triphosphate (ATP) and neuropeptide Y (NPY).

Renal vascular resistance properties and glomerular protection in early established SHR hypertension.

To characterize the in vivo vascular properties of the spontaneously hypertensive rat (SHR) renal vascular bed by examining vascular conductance/resistance responsiveness to vasoactive agents in vivo and determining whether the filtration surface area of glomerular capillaries is reduced. in vivo renal blood flow responses to intrarenally administered angiotensin II, phenylephrine and acetylcholine were compared in 10-week-old SHR and Wistar-Kyoto (WKY) rats using a wide range of doses from near threshold to near maximal effect. Unbiased stereological techniques and high-resolution light microscopy were used to estimate the surface area and length of glomerular capillaries, and evidence of capillary damage. The SHR renal bed demonstrated significantly enhanced dose-vascular resistance responses to vasoconstrictors. For vascular conductance and calculated radius of resistance vessels, the SHR curves were significantly lower across the full dilator-constrictor range examined, but the dose-related changes were similar to those of WKY rats. There were only modest enhancements of the renal blood flow responses in the SHR, evident only when renal blood flow was reduced by more than 50% SHR and WKY rats did not differ in mean glomerular capillary surface area (0.13+/-0.02 mm2 and 0.14+/-0.02 mm2, respectively) or length (5.76+/-0.85 mm and 5.48+/-0.90 mm, respectively) nor was there evidence of glomerular capillary damage in either strain. The renal vascular bed of the SHR in vivo exhibits reduced vascular conductance across a wide vasomotor range, compatible with findings in other vascular beds. We have further shown no evidence of reduced glomerular capillary surface area or damage. These findings are compatible with the hypothesis that the reduced conductance of the SHR pre-glomerular vasculature increases the aorta-capillary pressure gradient thus protecting the glomerular capillaries from systemic hypertension at this age.

Histopathological evidence of poor prognosis in patients with vesicoureteral reflux.

Patients with vesicoureteral reflux (VUR) often develop reflux nephropathy with focal segmental glomerular sclerosis (FSGS), although the exact mechanisms leading to the development of this complication are unknown. To determine the early changes in glomeruli of VUR patients that ultimately cause poor renal outcome, we examined morphometrically renal biopsies of 16 young patients (age 10-20 years) with VUR at baseline pre-operatively. Patients were divided into two groups, those who subsequently showed good prognosis and those with poor renal prognosis at the end of a 10-year follow-up period. Patients with poor prognosis had worse proteinuria and lower creatinine at baseline than those with good prognosis. We also examined 40 age-matched control cases with previous temporal microhematuria and/or proteinuria but normal renal function and histology. Although the mean diameter of glomerular capillary did not change in VUR cases irrespective of prognosis, glomerular capillary length increased by 125% in cases with good prognosis, and 335% in cases with poor prognosis (P < 0.01). Cystically expanded capillaries, with diameter > or = 95% of that in age-matched control, were detected in five of eight patients with poor prognosis, but only in one of eight patients with good prognosis. In VUR, the number of podocytes/capillary diminished with increased length of the capillaries. Tuft adhesion to Bowman's capsule and podocyte detachment were primarily found in patients with poor prognosis. Our results suggest that lengthening of glomerular capillaries in young patients with VUR is a compensatory reaction to hyperfiltration. The appearance of cystic capillary expansion, podocyte detachment and/or tuft adhesion to Bowman's capsule in such glomeruli may be important indicators of renal prognosis in patients with VUR. These changes may lead to FSGS due to podocyte injury in patients with VUR, with subsequent deterioration of renal function.

Effects of maternal bilateral ureteral ligation on fetal development of kidney in rats: Morphometrical changes in glomerular components

Development of the glomerulus in fetal kidney was studied morphometrically following ligation of both ureters of pregnant rats. The ligation was performed on days 17, 19, and 21 of gestation, and autopsy was done 24 hr after each operation. The percentage volumes of the five glomerular components (epithelial cells, capillary, mesangium, glomerular basement membrane, and Bowman's space) were determined by point counting, and the surface area of glomerular basement membrane per unit volume of glomerulus was calculated by intercept counting. On fetal days 18, 20, and 22, percentage volume of Bowman's space in the fetuses from the ligated mothers was significantly smaller than that in the fetuses from sham-ligated mothers. On fetal days 20 and 22, surface area of glomerular basement membrane and glomerular capillary length per unit volume of glomerulus and percentage of glomerular capillary volume in the fetuses from the ligated mothers were significantly larger than those in the fetuses from sham-ligated mothers. These results suggest that maternal bilateral ureteral ligation induces an increase in filtration area of glomerulus in fetal kidney when the fetal kidney is functional.

The Quantitative Development of Glomerular Capillaries in Rats with Special Reference to Unbiased Stereological Estimates of Their Number and Sizes

The kidneys of 14 female Wistar rats from 5 days to 18 months postnatally have been perfusion-fixed to study the development of glomerular capillaries using design-based stereological techniques. This report uses a topological definition of a capillary structural unit which forms the basis for the estimation of the number of glomerular capillaries using histological sections. The number of mature glomeruli is about 27,500 for all animals older than 5 days, whereas the 5-day-old animals have 21,100 mature glomeruli. Postnatally, the mean glomerular volume increases rapidly for the first 2 months after which it increases at a much slower rate. At first there is a rapid increase in total number, length, and surface area of glomerular capillaries with age; after 2 months the increase is rather moderate. The rapid growth of glomerular capillaries is anisomorphic, and the restrained growth is roughly isomorphic. The mean length of glomerular capillaries is nearly constant at 56 μm in mature and immature rats. The cross-sectional area rises only twofold from the most immature to the oldest rats. Using an approximation of the geometric factor in the law of Poiseuille, a decreasing resistance of glomerular capillaries with age is obtained. This is in agreement with the falling resistance of maturing renal vasculature and the increasing single-nephron glomerular filtration rate. When taking into account the constant mean capillary length and moderate increase in cross-sectional area of glomerular capillaries in growing rats, it appears that the branching of capillaries, forming a complicated network of serial and parallel connections, seems to be the structural basis for normal glomerular capillary growth.

Number and dimensions of rat glomerular capillaries in normal development and after nephrectomy

Glomerular capillary growth was studied in kidneys in five- to 540-day-old perfusion-fixed normal or sham-operated rats (C) as well as in unilaterally nephrectomized three-day-old (NN) and 120-day-old (NA) rats. The number and volume of mature glomeruli were estimated using the fractionator. The glomerular number was unaffected by neonatal or adult nephrectomy, but the number of mature glomeruli in all rats aged five days (19.1 +/- 2.0 x 10(3); +/- SD) was significantly smaller than for all the older animals (26.5 +/- 3.1 x 10(3)). The mean glomerular volume increased 59% and 20% for the NN and NA rats, respectively, versus the C rats. A capillary unit has been defined according to the number of loops in the glomerular capillary network by the use of topology. Glomerular capillary number, estimated using a physical disector, increased 53% for NN rats and 26% for NA rats. The glomerular capillary length was estimated on isotropic, uniform random sections, and increased 47% for NN rats and 12% for NA rats. The glomerular capillary surface area increased 54% for NN rats and 14% for NA rats. The diameter of the glomerular capillaries increased 8% for the mature NN versus the C rats. The rather unexpected findings are discussed and related to interesting relationships, including the law of Poiseuille and LaPlace. In conclusion, the growth of glomerular capillaries after neonatal and adult nephrectomy is performed by branching that is making new glomerular capillaries, instead of simply lengthening the existing capillaries.

The effect of hypertension on glomerular structures and capillary permeability in passive Heymann glomerulonephritis

In glomerulonephritic and normal kidneys hypertension has been shown to increase the urinary protein excretion and the thickness of the glomerular basement membrane and to reduce the glomerular filtration rate. We have studied the effect of desoxycorticosterone acetate (DOCA)-salt hypertension on the glomerular anatomy and function in normal control rats and rats with passive Heymann nephritis. Standard methods for measurements of glomerular filtration rate and urinary protein excretion were used and the results were correlated to morphometrical measurements in randomly selected glomeruli in all groups. In control rats, DOCA-salt hypertension increased the kidney weight ( P < 0.001), the glomerular volume ( P < 0.05), and the surface of peripheral glomerular basement membrane ( P < 0.01). The thickness of peripheral glomerular basement membrane and the length of glomerulary capillaries were not affected. In glomerulonephritic rats, DOCA-salt hypertension did not change the kidney weight and glomerular capillary diameter. The thickness of the peripheral basement membrane increased ( P < 0.05), while the length of glomerular capillaries and the surface of peripheral basement membrane were reduced ( P < 0.05). Glomerular filtration rate per unit peripheral basement membrane was not significantly different among the groups while protein excretion per unit peripheral basement membrane increased significantly both in the hypertensive and in the glomerulonephritic groups. The estimated hydraulic conductivity of the glomerular capillaries was reduced both in rats with DOCA-salt hypertension and in glomerulonephritic rats with and without DOCA-salt hypertension. In conclusion, DOCA-salt hypertension seems to decrease hydraulic conductivity and increase protein excretion both in normal and in glomerulonephritic kidneys although the effect on glomerular morphology is different.