Susanne Mackensen-Haen

Significance of Tubulointerstitial Changes in the Renal Cortex for the Excretory Function and Concentration Ability of the Kidney: A Morphometric Contribution

This is an editorial review of investigations into the correlation of structure and function of the kidney in various inflammatory and noninflammatory glomerular diseases and in focal and diffuse interstitial nephritis. In detail these investigations produced the following results: (1) The excretory function of the glomeruli for substances usually eliminated with the urine is, in the case of inflammatory and noninflammatory glomerular diseases, detrimentally affected by tubulointerstitial changes, i.e. by processes accompanied by interstitial fibrosis and tubular atrophy. Likewise primary interstitial renal diseases when accompanied by interstitial fibrosis and tubular atrophy may lead to reduction in GFR. (2) Inflammatory and noninflammatory glomerular diseases, even when very severe, are not accompanied by a measurable reduction in GFR when the renal cortex interstitium shows no changes and the tubules exhibit no pathological findings. (3) The concentration ability of the kidney, too, depends primarily on tubulointerstitial changes and not primarily on a reduction of the glomerular filtration surface area. As interstitial fibrosis and tubular atrophy increase, the maximum concentration ability of the kidney decreases, even when the glomerular structure is preserved. (4) The decrease in GFR in the case of processes in the renal cortex accompanied by severe interstitial fibrosis is the result of the reduction of the number and of the area of the postglomerular vessels, i.e. the result of an impeded outflow from the glomeruli and of a concomitant slower circulation through the glomeruli. (5) In the case of inflammatory and noninflammatory glomerular and extraglomerular renal diseases accompanied by slight interstitial fibrosis and tubular atrophy, the GFR is detrimentally affected via a hormonally controlled self-regulating mechanism (Thurau-mechanism) in the form as modified by Baumbach and Skott and Leyssac. The glomerular function thereby adapts to an insufficient tubular function, without there necessarily being any structural changes in the glomeruli.

The obliteration of the postglomerular capillaries and its influence upon the function of both glomeruli and tubuli

SummaryOur study in a group of patients (heterogeneous in terms of glomerular lesions), supplementing and confirming earlier findings, indicated that1.An increase of the relative cortical interstitial volume and the serum creatinine concentration at the time ob biopsy is accompanied by a statistically significant reduction in the number of intertubular capillaries and a decrease in capillary area per area unit.2.The length of diffusion between the intertubular capillaries and tubuli increases and the tubular epithelium becomes atrophic as relative cortical interstitial volume increases.3.The glomerular capillaries and the Bowmans capsule are significantly larger in moderately severe mesangioproliferative or grades I to III membraneous GN with elevated serum creatinine concentrations than in equally severe renal diseases with normal serum creatinine concentrations.4.The glomerulus in moderately severe mesangioproliferative GN progressively increases as the serum creatinine concentration rises. On the basis of these findings, it was concluded that the increase of the cortical interstitial volume results in an increase in resistance of the postglomerular capillary network with impairment of the glomerular flow. This impairment leads to a functional or, to be more precise, a chronic rise in hydrostatic pressure and also to a reduction in the glomerular blood flow and therefore a rise in serum creatinine concentration. The chronic rise in hydrostatic pressure also results in an increase in the size of the glomerulus. The increase of the cortical interstitium additionally leads to an increase in the length of diffusion between the tubules and the intertubular and peritubular capillaries. This increase in the length of diffusion subsequently results in atrophy of the tubules, reduction of reabsorption, and therefore impairment of the effective filtration pressure.ZusammenfassungVorliegende Untersuchungen führen in Ergänzung und Bestätigung früherer Untersuchungsergebnisse an einem im Hinblick auf die glomerulären Läsionen heterogenen Untersuchungsgut zu folgenden Resultaten:1.Eine Zunahme des relativen Nierenrindeninterstitiumvolumens bzw. der Serumkreatininkonzentration zur Zeit der Biopsie geht mit einer statistisch signifikanten Abnahme der Anzahl der intertubulären Kapillaren und der Kapillarfläche pro Flächeneinheit einher.2.Mit der Zunahme des relativen Nierenrindeninterstitiumvolumens nimmt die Diffusionsstrecke zwischen intertubulären Kapillaren und Tubuli zu und die Tubulusepithelien werden atrophisch.3.Bei mittelschwerer mesangioproliferativer Glomerulonephritis bzw. membranösen Glomerulonephritiden Schweregrad I–III ist das glomeruläre Kapillarkonvolut und die Bowmansche Kapsel bei erhöhter Serumkreatininkonzentration signifikant größer als bei gleich schweren Erkrankungen mit normaler Serumkreatininkonzentration.4.Bei mittelschwerer mesangioproliferativer Glomerulonephritis nimmt das glomeruläre Kapillarkonvolut mit steigender Serumkreatininkonzentration zu. Aus diesen Befunden wird gefolgert, daß es durch die Verbreiterung des Nierenrindeninterstitiums zu einer Erhöhung des Widerstandes in der postglomerulären Kapillarstrecke kommen muß mit Beeinträchtigung des Abflusses aus den Glomerula. Diese Abflußbehinderung führt funktionell zwar zu einer chronischen Steigerung des hydrostatischen Druckes in den Glomerulumkapillaren, jedoch auch zu einer Reduktion der Glomerulumdurchblutung und damit zum Kreatininanstieg. Bedingt durch die chronische Steigerung des hydrostatischen Druckes kommt es ferner zu einer Zunahme des Kapillarkonvolutes (Erweiterung der Kapillaren, vermehrter Einbau von Kollagen, u.a. in die Kapillarwände). Ferner führt die Verbreiterung des Nierenrindeninterstitiums zu einer Zunahme der Diffusionsstrecke zwischen inter- bzw. peritubulären Kapillaren und Harnkanälchen mit konsekutiver Atrophie der Kanälchen und einer Reduktion der Rückresorption und einer dadurch bedingten Beeinträchtigung des effektiven Filtrations-druckes durch Anstieg des hydrostatischen Druckes im Bowmanschen Kapselraum.

The Consequences of Tubulo-Interstitial Changes for Renal Function in Glomerulopathies

In recent years it has become recognized to an increasing extent that a wide range of inflammatory and non-inflammatory glomerular diseases may be complicated with varying frequency by disease in the region of the post-glomerular intertubular capillaries. Thus we found additional disease of the tubulo-interstitial system in 4.0 – 69.5% of patients with the diseases listed in Table 1. Amongst these diseases, accompanying inflammation of the renal cortical interstitium occurs least often in endocapillary glomerulonephritis and most often in diabetic glomerulosclerosis. Amongst the glomerulonephritides, interstitial inflammation leading to fibrosis is observed most frequently in rapidly progressive glomerulonephritis and membranoproliferative glomerulonephritis. Interstitial inflammation is found relatively often in glomerular amyloidosis. As a result of investigations we have undertaken in the last three years, it has been possible to demonstrate that the character of the inflammatory interstitial changes that accompany glomerular diseases is always the same, no matter what the glomerulopathy may be. The cells most predominantly involved in the inflammatory process are T lymphocytes, macrophages, fibroblasts and fibrocytes. Thus dense foci of T lymphocytes and macrophages are seen not only in Table 1 Survey of the incidence of intertubular inflammation associated with interstitial fibrosis in various glomerulopathies. Various Glomerulopathies And The Occurrence Of Interstitial Inflammation And Interstitial Fibrosis Total Number Of Casas Cases With Interstitial Fibrosis (%) 1) Endocapillary GN 137 4.0 2) Minimal Changes With NS 470 8.5 3) Focal Sclerosing GN 469 34.1 4) Mesangioproliferative GN 805 23.0 a) Immunologically Negative GN 238 13.9 b) IgA Nephritis 369 23.3 c) Non-lgA Nephritis 198 33.3 5) Chronic Idiopathic Membranous GN 642 23.8 6) Membranoproliferative GN Type I 259 41.0 7) Rapidly Progressive GN 208 56.7 8) Perireticular Amyloidosis 443 48.0 9) Diabetic Glomerulosclerosis 406 69.5 mesangioproliferative glomerulonephritis, but also in the interstitial inflammation that complicates renal amyloidosis. The tubulo-interstitial inflammation of diabetic glomerulosclerosis is also characterized by T lymphocytes, macrophages, fibroblasts and fibrocytes.

Molecular and cytogenate analysis of an X/autosomal translocation: 45, X, dic(X;17)(p22.2;p13)

We present an unusual case of monosomy 17p13‐pter and monosomy Xp22.2‐pter due to a dicentric translocation chromosome X/17 in a female newborn with severe anomalies. The karyotype was identified as 45, X, dic(X;17)(p22.2;p13) by high resolution GTG banding in lymphocytes. R banding showed the translocational X‐chromosome to be late replicating, and there was no spreading of X‐inactivation onto the autosomal segment. Furthermore, it could be demonstrated by C banding that the X‐centromere in the translocation chromosome was inactive.