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Renal complications occur frequently in diabetics. Glomerular lesions exist in basal membrane thickening, diffuse and nodular glomerulosclerosis, exudative lesions and glomerular aneurysms. Tubular and interstitial changes are characterized by Armanni-Ebstein cells, by pyelonephritis and papillary necroses. Vascular changes occur in the form of arteriosclerosis and arteriolosclerosis. Nodular glomerulosclerosis is characteristic of diabetic renal damage, all other changes only occur more frequently in diabetics. Recently, studies deserve attention which suggest a regression of glomerular lesions if the diabetic metabolism is normalized.

Morphology of nephrosclerosis at its early stage is characterized by nosologic specificity. Morphogenetic mechanisms of glomerulosclerosis vary greatly and depend on the specific feature of the disease pathogenesis, underlying nephrosclerosis. Stromal sclerosis of renal cortex stroma is associated with the increase in collagen-synthesizing function of interstitial fibroblasts. At the late stages of nephrosclerosis all renal tissue structures are equally affected with sclerosis, resulting in loss of nosologic specificity of the process. Arterial hypertension favours the progression of nephrosclerosis.

Using semiquantitative morphometric methods, the clinical picture of decompensated benign nephrosclerosis is distinguished from that of secondary malignant nephrosclerosis, designated as the consequence of high pressure. It is shown that hypertensive glomerulopathy triggered by high pressure and postglomerular interstitial fibrosis with tubular atrophy are in the foreground of pathologic changes in decompensated benign nephrosclerosis, whereas the preglomerular vessel network is most often affected in secondary malignant nephrosclerosis. The preglomerular vascular lesions in secondary malignant nephrosclerosis lead to such heavy stenosis of the afferent vessels that the clinical picture of hypertensive glomerulopathy is rarely observed, while that of ischemic glomerular capillary collapse is frequent. The preferred affliction of the glomeruli and the postglomerular vessel network leads in decompensated benign nephrosclerosis to severe interstitial fibrosis, which has a pyramidal form, decreasing from the base of the pyramid at the corticomedullary boundary to the outer renal cortex. In secondary malignant nephrosclerosis fibrosis of the renal cortical interstitium is homogeneous in all layers of the renal cortex. Clinically, decompensated benign nephrosclerosis and secondary malignant nephrosclerosis, which occur predominantly in young to middle-aged males, manifest malignant hypertension. They are also accompanied by progressive renal insufficiency.

Eleven patients with malignant arterial hypertension and malignant nephrosclerosis, verified by percutaneous renal biopsy, were examined during an observation period of 47 months (median). All patients received antihypertensive therapy. Patients were divided into three groups with regard to development of renal function during the observation period. In two patients (group I), the integrated average blood pressure (IA-BP) was 134/95 mmHg (median) and the calculated creatinine clearance (Ccr) increased from 19 to 56 ml/min (medians). In four patients (group II), IA-BP was 154/102 mmHg and Ccr remained stable-at approximately 60 ml/min. In five patients, (group III), IA-BP was 189/114 mmHg, owing to lack of patient compliance and absence from regular control, and Ccr was reduced from 26 ml/min to less than 5 ml/min. During the first 2 months of antihypertensive therapy, renal function was temporarily reduced in 7 of the 11 patients. It is concluded that effective blood pressure control in patients with malignant arterial hypertension and malignant nephrosclerosis can be accompanied by a considerable improvement, or at least a preservation of renal function.

The development of a precise, mathematical relationship between blood pressure and renal microvascular abnormalities would be highly desirable. Such a relationship would require that abnormalities be quantitative on a rational scale. The dominant abnormality in nephrosclerosis occurs in arcuate and cortical arteries of 50 to 400 micron outer diameter. This abnormality consists of acquired inner layers of fibroplastic tissue accompanied by variable fibrosis or withering of the preexisting vessel wall. It is this pathologic variable of interest, the amount of fibroplasia, that can be measured by its thickness in a direction perpendicular to the arterial axis. A method for quantitating the fibroplasia is described. Use of this method in a series of 93 autopsies suggests two tentative conclusions. The outer diameter of 141 micron marks the size of artery in which fibroplasia best correlates with blood pressure. The linear function, mean blood pressure = 1.60 X microvascular lesions +79.7, with correlation coefficient 0.698, governs a relationship similar at all ages. This relationship can be used to compute expected blood pressure from measurements of microvascular abnormalities in kidneys obtained at autopsy. Because all ages include ages 14 to 21 years, the observations imply that the initial tissue changes of hypertensive disease occur early in life.

Decompensated benign nephrosclerosis, a disease which was briefly described by Theodor Fahr in 1925, defended by him in 1934, and then forgotten, is reported and differentiated from compensated benign nephrosclerosis. Decompensated benign nephrosclerosis can be differentiated from compensated benign nephrosclerosis by the frequent appearance of interstitial cortical fibrosis and glomerular alterations in the sense of hypertensive glomerulopathy. Hypertensive glomerulopathy results in ascending obliteration of the glomeruli, i.e., their transformation into PAS-positive hyaline globules. In compensated benign nephrosclerosis, interstitial fibrosis, if present at all, can usually be identified only in the subcapsular areas. In decompensated benign nephrosclerosis, however, a pyramid-like structure with its base at the corticomedullary border is formed. The severity of preglomerular vascular alterations does not differ in compensated and decompensated benign nephrosclerosis. Clinically, there is no significant difference between the degree of hypertension and the development of the disease. The nephritic symptoms are more pronounced in decompensated benign nephrosclerosis, which predominantly affects middle-aged men (male:female, 5.7:1), than in compensated benign nephrosclerosis. As a result, decompensated benign nephrosclerosis is frequently diagnosed and treated as chronic glomerulonephritis.

A glomerular disease spontaneously developing in Wistar rats was studied by light and electron microscopy and by immunofluorescence techniques. The disease is characterized by the local subendothelial deposition of hyaline material leading to increase of mesangial matrix and the development of adhesions. Immunofluorescence shows deposition of complement and IgM and to a lesser degree also of IgG in these lesions. There is a constant relationship of these early changes with the vascular pole of the glomerulus. It is confirmed that female rats are resistent to the disease as are male rats fed a sodium-deficient diet. A higher protein excretion was found in normally fed male rats as compared to female rats and to rats on a sodium-deficient diet. These differences already existed before the normally fed male rats developed glomerular disease. From these studies it is suggested that an appropriate name for this disease would be focal and segmental glomerular hyalinosis and sclerosis and that hemodynamic factors could be an important etiologic mechanism. The histopathology of the disease bears a striking resemblance to focal sclerosing glomerulopathy with segmental hyalinosis sometimes found in kidneys of patients with an idiopathic nephrotic syndrome.

Heavy metal nephropathy is a pathologic entity of the renal tubular epithelium of rats, evoked by lead, gold, and other heavy metals. It is characterized acutely by coagulative necrosis, subacutely by cortical fibrosis, and chronically by cytomegaly and karyomegaly. Finally, adenomas develop, some of which become malignant.

A chronic renal disease was induced by 5/6 nephrectomy in young adult Wistar albino male rats. Groups of 3 rats were killed at varying time intervals from 10 to 50 weeks after nephrectomy, and the glomerular structure was studied by light and electron microscopy. By light microscopy, increase in glomerular size and hypertrophy of the visceral glomerular epithelial cells were evident as early as the tenth week. Significant degree of glomerular hyalinization started on the 25th week and gradually became more extensive in involvement towards the 50th week. By electron miscroscopy, the hypertrophied glomerular epithelia showed many osmiophilic bodies and vacuoles in their cytoplasm and fusion of foot processes. Beginning on the 30th week, increase of the mesangial matrix was quite evident, and endothelial and epithelial cells disappeared from the areas where the increase was prominent. The increased matrix gradually encroached and occluded capillary lumina and Bowman's space, leading to a formation of obsolescent glomeruli. Whether or not these glomerular changes are due to the glomerular hyperfiltration which has been known to occur after 5/6 nephrectomy remains to be elucidated.

Nephrosclerosis, the morbid condition of the kidney that accompanies essential hypertension, is characterized by thickening of the walls of cortical arteries. According to the law of Laplace, the tension in the wall of an artery should be proportional to the product of pressure (P) times diameter (D). Thus, if wall thickness (T) is governed by wall tension, then it should be proportional to the same product: T = kPD, where k is a proportionality constant. A comparison of immersion-fixed kidneys in normotensives aged 75 to 90 years with those aged 19 to 34 years showed the magnitude of k to increase with age. The increase was 41% in vessels that were relatively close to the heart (outer diameter, 150 to 300 microns) and 30% at the more remote level (outer diameter, 80 to 140 microns). In perfusion-fixed specimens, k also increased with age, being 77% and 35% greater, respectively, for the comparison between normotensives in the two age groups. Normotensives were defined to be those with mean blood pressure less than 115 mm Hg. A similar result was found by defining normotension to be systolic pressure less than 140 mm Hg. Wall thickness was not proportional to pressure in hypertensive compared with normotensive subjects, but rather to a quadratic function that combined age and blood pressure taken together. The law of Laplace did not fully encompass the data that relate the thickening of renal arterial walls to hypertension or to aging in the absence of hypertension. The thickening with age is structurally a metaplasia that exchanges fibrotic intima in the elderly for muscular media in the young. The result was reproduced in perfusion- as well as immersion-fixed specimens and is therefore not distorted by postmortem collapse. The results favor the conclusion that arterial wall thickening in hypertensive and aging normotensive kidneys is sclerosis and not adaptive hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal glomerular sclerosis (FGS) with the nephrotic syndrome is a disecades. Less than 2% of reported patients are older than 60 years of age, and to our knowledge no patients over 70 years of age have been described. The present report documents with renal biopsies the occurrence of FGS and the nephrotic syndrome in 4 patients with an average age of 70 years, 3 being septuagenarians. We suggest that FGS in these patients may represent a disease of senescence, and that FGS in younger patients may result from accelerated glomerulotubular senescence.

The term "Endotheliotropic Hemolytic Nephroangiopathy" (EHN) comprises various clinically or pathomorphologically defined disease states with severe renal lesions (e.g. hemolytic uremic syndrome, malignant nephrosclerosis, post partum renal insufficiency) which, to date, have been considered as different entities. We attempted to assign accompanying glomerular changes based upon light and electron microscopy to the above mentioned clinical pictures and their various stages. The accordingly classified glomerular lesions (G1--G3 and Ga) are of critical importance in pathohistological differential diagnosis. Since it is assumed that fibrin is a causing event in the pathogenesis of the vascular lesions, quantitative evaluation of glomerular fibrin deposits was done. The results, when viewed with respect to time, lead to the conclusion that the microthrombotic component represents a secondary phenomenon. Thus, the primary and hence pathogenetically most important finding is a severe damage to the endothelium of the terminal renal vasculature. This endothelial damage although being expressed with variable intensity has to be regarded as the common denominator inherent to all types of glomerular lesions in EHN.

Many patients with chronic pancreatitis (CP), even in the absence of intrinsic renal disease, are found to have abnormal urine, with persistent proteinuria, cylindruria, microhematuria and leukocyturia. The kidneys of 12 necropsy cases with CP showed mild to moderate arterial and arteriolar nephrosclerosis and no other significant changes. Renal biopsies were performed in 10 patients with CP without evidence of systemic disease or intrinsic renal disease, but with persistent urinary abnormalities. By light microscopy, mild arterial and arteriolar nephrosclerosis was present in 5 instances. In 1 patient, evidence of the reparative phase of acute tubular necrosis was noted. In 5 biopsies, electron microscopy revealed minimal to mild increase in mesangial matrix. Mild thickening of the glomerular basement membrane (GBM) was found in three instances but there was no clear-cut evidence of diabetic glomerulosclerosis. The presence of subendothelial electron-lucent material in 3 cases suggests the possibility of previous subclinical episodes of intravascular coagulation. The most consistent finding was the presence of lipid material in the cytoplasm of glomerular and tubular cells. The renal lesions associated with CP are mild, nonspecific and nonprogressive. Various pathogenetic factors can be invoked to account for their presence and for the urinary abnormalities found in patients with CP.

It had been previously thought that protein excretion in hypertensive nephrosclerosis was less than 0.5 to 1.0 g/24 h. Furthermore, it was believed that proteinuria in the nephrotic range associated with hypertension was probably due to primary renal disease, malignant hypertension, renal artery stenosis, or pheochromocytoma. We report eight patients with biopsy-proven hypertensive nephropathy and heavy proteinuria in the absence of malignant hypertension or renal artery stenosis. The 24-hour protein excretion ranged from 2.7 to 4.3 g. All patients had renal insufficiency, with serum creatinine ranging from 2.0 (176.8) to 7.8 mg/dL (689.5 mumol/L). Renal function worsened in most patients during the follow-up period despite adequate control of the hypertension, and three patients had to be started on hemodialysis. Three patients died during the follow-up period. We conclude that hypertensive nephrosclerosis must be included in the differential diagnosis of marked proteinuria in patients with essential hypertension and that heavy proteinuria, along with renal insufficiency, are poor prognostic indicators in such patients.

Glomerular changes were morphometrically studied in renal biopsies of 27 cases of nephrosclerosis showing clinically benign or malignant hypertension and of 15 cases of mild mesangioproliferative glomerulonephritis with hypertension. In nephrosclerosis, there was a mild increase in mesangial matrix without cell proliferation. The degree of the mesangial changes varied little despite a large variation in blood pressure and showed no significant difference between benign and malignant hypertension. In mild mesangioproliferative nephritis with hypertension, mesangial matrix, as well as the number of mesangial cells, showed an increase of varying degree. A quantitative assessment of the mesangium was proved effective in differentiating the glomerular changes in nephrosclerosis from those in mesangioproliferative nephritis with hypertension.

The case is presented of a young girl with recurrent urinary tract infection and vesico-ureteric reflux who developed a small scarred kidney and subsequently, hypertension. Pathologically, the renal changes were compatible with those of an Ask-Upmark kidney. The pathogenesis of the Ask-Upmark kidney is discussed. It is postulated that the lesion is not necessarily of congenital origin but may well be related to infection and intrarenal reflux, it is concluded that long-term follow-up of a young patient with a scarred kidney is indicated.

The concept of acute renal failure with anuria due to malignant nephro-angiosclerosis, is uncommon. We report two cases and compare them with others in the world literature. Knowledge of this disease entity is of triple interest: In diagnosis and classification in the field of acute vascular nephropathy with anuria. We cannot emphasise too much the interest of early renal biopsy after correction of abnormal blood pressure. In physiopathology, these malignant nephro-angioscleroses give rise to hypertension of pressor type with high renin levels. Finally therapeutic, for there exist drugs adapted to this type of hypertension. The association of acute renal failure and malignant nephro-angiosclerosis should be treated as an emergency, to avoid the passage to terminal and irreversible renal failure.

The term diabetic nephropathy includes the Kimmelstiel-Wilson intercapillary glumerulosclerosis (1936), arterio-arteriolosclerotic changes and pyelonephritis. In principle, diabetic nephropathy becomes more frequent with increasing duration of diabetes mellituus. Pyelonephritis is 4 to 5 times more frequent in diabetics than in the general population. Elderly overweight women are particularly at risk. - Only the nodular intercapillary glomerulosclerosis and not the diffuse or exudative form is specific for diabetes mellitus. It is found in 20-40% of all diabetics who have had the disease for 10-15 years. Whether the microangiopathy is typical of diabetes mellitus remains to be seen. Due to the intense cardiovascular changes, possible disorders of brain and liver function and infection, the prognosis of renal insufficiency is considerably worse in diabetics than in non-diabetics.

Angioblastic-appearing nodules of small arteries of heart, pancreas, and kidneys were found during microscopic study of autopsy specimens form subjects with hypertension that had responded poorly to treatment. These vascular lesions were noted in three of 15 subjects studied; they were associated with a proliferative arteriolosclerosis that was most severe in the kidney and the pancreas, but was occasionally found in the arterioles of the heart. Two of these three subjects had received treatment with dialysis; one had not. The nodules originated concentrically along a segment of small artery and consisted of a mass of mesenchymal cells and capillary-sized blood channels. There were fragmentation and focal loss of the internal elastic lamina at their points of origin, and vessel-wall necrosis in an occasional lesion. Many of these nodules appeared identical to plexiform lesions of the lung and to cellular types of Charcot-Bouchard aneurysms of the CNS.

Renal biopsies from 40 patients with hypokalemia and hyponatremia of an average of 10 years' duration due to abuse of laxatives or diuretics, anorexia nervosa, or chronic vomiting were examined with morphometric methods. Light microscopy revealed the following alterations in the renal cortex as compared with 36 normal kidney: JGC were sometimes slightly and sometimes enormously enlarged (mean, 217%). Smaller glomeruli were found with reduction in the area of the glomerular capillaries and of Bowman's capsule (+/- 7%) but an increase in the area of the mesangial matrix by 25%. The proximal and distal tubules contained nonspecific vacuoles in only 8 of 40 biopsy specimens. Only minor, age-dependent arteriolosclerosis was demonstrable. In 75% of the cases, the interstitial surface area was increased (by 107%) with predominantly focal lymphocytic cellular infiltration. Interstitial fibrosis was more pronounced in emaciated patients. The morphologic-functional correlation between the increase of interstitial surface area and the rise in serum creatinine concentration was highly significant. Typical kaliopenic nephropathy is therefore detectable by light microscopy. GFR impairment correlates with the extent of interstitial fibrosis.

Electron microscopic analysis of subendothelial and mesangial alterations in the glomeruli was performed in 15 cases of malignant nephrosclerosis (MNS). 8 cases showed segmental or diffuse subendothelial accumulation of proteinaceous 'fibrinoid' material associated with thickening of glomerular basement membranes. 2 of these cases also showed similar deposits in the mesangium. When severe, this mesangial insudation resulted in almost complete replacement and destruction of the mesangial matrix. Endothelial injury with alteration of glomerular microcirculation and secondary intravascular coagulation is believed to play a role in the development of the glomerular lesions in MNS.

A case of a man suffering from psoriasis vulgaris is presented. The onset of the disease was at the age of 5. From the age of 14 all joints were gradually affected by the type of severe, symmetrical psoriatic arthritis which led to aseptic necrosis of the hip joints. In the course of the disease, from 1988 on, proteinuria and nephrotic syndrome were found. The renal biopsy proved amyloidosis which is considered secondary, developed on the basis of psoriatic arthritis. The severe psoriatic arthritis with especially emphasized clinical activity is in this case the pathologic antigenic stimulus for the amyloid formation. The clinical course and the histologic findings from the renal biopsy point to serious structural disorders of the renal parenchyma which determine the progressing tendency toward chronic renal failure.

Morphometrical investigations (point-counting method) showed that in different inflammatory (endocapillary -- acute -- GN, mesangioproliferative GN, membranoproliferative GN) glomerulonephritides and in non-inflammatory glomerular diseases (perireticular amyloidosis), there are statistically significant correlation between serum creatine concentrations at the time of biopsy and the enlargement of the cortical interstitium by fibrosis. Similar results were obtained in investigating different grades of benign nephrosclerosis with transition into secondary malignant nephrosclerosis conditioned by hypertension and in chronic diffuse sclerosing interstitial nephritides of different etiologies. As hypothesis, we assume that a narrowing of the postglomerular vessel network by interstitial fibrosis take place. This could lead to an increase resistance of the renal cortical blood flow. In spite of an elevated effective filtration pressure, the slowing of the glomerular blood flow may lead to the reduction of GRF and to an increase of the serum creatinine concentration. Additionally, in the case of interstitial fibrosis the tubules look atrophied. This could be the consequence of the reduced GFR as a sign of inactivity. On the other hand, tubular atrophy could result from malnutrition in the case of interstitial fibrosis. The resorptive capacity of these atrophied-looking tubules could be lowered and the GFR could be diminished by the so-called Thurau mechanism.