The glomerulo-tubular junction: a target in renal diseases.

Both global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo-tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron.

Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus.

Human glomerular capillary tufts were removed by microdissection and scanning electron microscopy was used to examine the surface of the capillary tuft and the interior of its Bowman's capsule in order to identify connections between the tuft and capsule. Glomeruli were examined in histologically normal renal cortex from 12 kidneys removed for tumour and 12 renal allografts removed for end-stage rejection. In normal kidney, the glomerular tuft was connected to Bowman's capsule by single podocytes and their processes. At the vascular pole, these were predominantly associated with parietal podocytes which lined Bowman's capsule. At the tubular pole, occasional podocytic processes derived from the capillary tuft bridged Bowman's space and connected to Bowman's capsule where there were no parietal podocytes. These podocytic connections were also found in all rejected transplants, but in addition adhesions were identified which consisted of thicker connections between the tuft and capsule. At the vascular pole, tuft-to-capsule adhesions were found in all 12 kidneys; these were always associated with parietal podocytes. Tubular pole adhesions were identified in ten of the 12 transplants. They were associated with abnormal squamous cells, but not with parietal podocytes. When the capillary tuft herniated into the proximal tubule, the tuft sometimes formed an adhesion with the origin of the proximal tubule. These observations suggest that podocyte connections between the glomerular tuft and Bowman's capsule may be precursors of glomerular adhesions at the vascular pole. Since tuft-to-capsule adhesions at the vascular pole differ morphologically from those at the tubular pole, this may reflect different pathogenetic mechanisms at the opposite poles of the glomerulus.

Atubular glomeruli and glomerular cysts--a possible pathway for nephron loss in the human kidney?

Glomerular tufts were removed and scanning electron microscopy was used to study the interior of Bowman's capsule, in order to identify atubular glomeruli. Normal renal cortex was studied from six kidneys removed for tumour and six renal transplants removed for end-stage rejection. Atubular glomeruli occurred in normal renal cortex in less than 1 percent of glomeruli, but were more common in transplant nephropathy, representing up to 61 percent of glomeruli. Glomerular cysts were identified which also lacked a tubular connection. Both atubular glomeruli and glomerular cysts contained a contracted glomerular capillary tuft and in both, Bowman's capsule was lined mostly by parietal podocytes. It is suggested that atubular glomeruli may be precursors of the glomerular cysts. The glomerular tuft may produce filtrate which exits the glomerulus via the parietal podocytes on Bowman's capsule. In normal human kidney, the formation of atubular glomeruli by disconnection from the tubule may represent an alternative pathway for the gradual nephron loss that is associated with ageing. This process may be amplified in disease: disconnection from the tubule may be an important part of irreversible nephron damage in chronic allograft nephropathy.

A comparative study of the glomerular peripolar cell and the renin-secreting cell in twelve mammalian species.

The peripolar cell is a glomerular epithelial cell situated within Bowman's capsule at its vascular pole. It is believed to be a secretory cell which forms part of the juxtaglomerular apparatus. Scanning electron microscopy was used to perform a comparative study of the morphology and number of peripolar cells in twelve mammalian species. The number of renin-secreting cells in kidney sections stained by renin antibodies and immunocytochemistry was counted. There was a marked inter-species variation in the number, size and appearance of peripolar cells. They were largest and most abundant in sheep and goat and fewest in dog, cow and human. There was no correlation between the numbers of peripolar cells and renin-secreting cells. This does not support the view that the peripolar cell is part of the juxtaglomerular apparatus.

Immune complex deposition in Bowman's capsule is associated with parietal podocytes.

We have recently documented the presence of podocytes lining part of Bowman's capsule at the vascular pole, in adult human kidney. In this study, we describe the deposition of immune complexes in Bowman's capsule in association with these parietal podocytes. We examined 1 year's consecutive human renal biopsies (n = 170). Transmission electron microscopy (TEM) revealed 18 cases in which parietal podocytes were present. Of these 18, there were 11 cases of glomerulonephritis, in which immune complexes were demonstrated in the capillary tuft by both TEM and direct immunofluorescence microscopy. In seven of these 11 cases, TEM showed immune complex-type deposits in Bowman's capsule, always associated with parietal podocytes. These deposits were similar in size, appearance, and distribution to the deposits in the capillary tuft. By contrast, non-specific electron densities within Bowman's capsule were found beneath both squamous parietal cells and parietal podocytes. In four cases, Bowman's capsule also showed focal positive immunostaining for complement components and/or fibrinogen. Both parietal and visceral podocytes showed similar fusion of pedicles. We suggest that filtration through parietal podocytes may be responsible for immune complex deposition and subsequent damage to the vascular pole of the glomerulus in human renal disease.

Non-granulated peripolar cells exist in the rat glomerulus.

The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules.

ANF (99-126) and its propeptide, ANF (1-16) are secreted simultaneously from the human atrial myocyte.

We have raised antisera to two synthetic peptides representing different portions of the human pro-atrial natriuretic factor (ANF) molecule; one antiserum identifies active human ANF, the 28-amino-acid sequence on the C-terminal end of the prohormone [ANF (99-126)], and the other detects ANF (1-16), the first 16-amino-acid sequence at the N-terminal end of the prohormone. With ultrastructural immunocytochemistry we have studied the distribution staining for both peptides within the myocytes in surgically excised human auricular appendages. Most of the endocrine granules stained with equal density for both ANF (1-16) and ANF (99-126). Also, double immuno-staining techniques on the same tissue section showed that both the C-terminal peptide and the N-terminal peptide co-existed within the same endocrine granules. It has been shown that, like other endocrine cells, atrial myocytes secrete their stored peptides by exocytosis of their granules. Therefore, our observations suggest that both the main active hormone, ANF (99-126), and the N-terminal propeptide ANF (1-16) are secreted simultaneously from the cell.

New morphological evidence for the synthesis and storage of renin in the human kidney: an ultrastructural immunocytochemical study.

Using an antibody to pure human renin and the technique of ultrastructural immunocytochemistry we have localized renin in the granular epithelioid cells of three juxtaglomerular apparatuses and one interlobular artery. The staining reaction of the cells was the same in both sites: we found that crystalline protogranules, rounded membrane-bound granules and storage granules intermediate in morphology all stained positively for renin. We also demonstrated immunoreactive renin in dilated cisternae of rough endoplasmic reticulum in the granular cells in both sites. We present these observations as morphological evidence that granular epithelioid cells synthesize and store renin both in the juxtaglomerular apparatus and in the larger arteries in the kidney.

The immunocytochemical demonstration of renin in a juxtaglomerular cell tumour by light and electron microscopy.

This is a study of a juxtaglomerular cell tumour using an antibody to pure human renin and the peroxidase-antiperoxidase technique. We report the distribution of immunoreactive renin in the tumour visualized by light microscopy of both paraffin and resin embedded tissue sections. We found that the cells which contained most renin granules were endocrine-like cells in the parenchyma of the tumour. Ultrastructural immunocytochemistry showed that immunoreactive renin was present not only in crystalline protogranules and in round membrane bound granules, but also in intermediate forms.