There is considerable similarity in the morphologic expression of radiation nephritis in man and in the rat. In both species the cellular structures as well as intercellular substances are affected. The most sensitive elements are the tubular epithelium, glomerular endothelium, the glomerular mesangium, and subendothelial and endomysial basement membranes in the arterial walls. The characteristic separation of cells from basement membranes in the glomeruli and tubules is probably due to the damage of both the cells and the membranes. Subsequent degeneration of muscle cells in the arterial media and deposition of fibrin lead to fibrinoid necrosis and thrombosis. Within the range of 1500 to 10,000 rads the nature of radiation changes remains the same irrespective of dose. Higher doses merely accelerate and aggravate the lesions and increase the frequency of severe arterial damage.
There seems to be little doubt that FGS is a nonspecific lesion that represents one way in which the renal glomerulus responds to a variety of injuries. This is illustrated by the large number of diverse conditions with which the lesion is associated including various forms of glomerulonephritis, pyelonephritis, hereditary nephritis, and heroin usage. Nevertheless, there remains a relatively large isiopathic group which, though possibly heterogeneous, displays a number of characteristic clinical and pathologic features including the following: 1. Steroid-resistant nephrotic syndrome; 2. Hematuria and hypertension; 3. Normal serum complement; 4. Progressive renal insufficiency; 5. Typical pathologic lesion most common in or restricted to juxtamedullary cortex; 6. Absence of clearly defined evidence of immune complex deposition by immunofluorescent or electron microscopic studies; 7. Recurrence of the lesion following renal transplantation. The pathogenesis of these changes is unclear, the evidence for an immune complex mechanism meager, and the suggestion that the disease is mediated by a humoral mechanism remains to be explored. The potential recurrence of this lesion in the transplanted kidney affords a unique opportunity to study the disease early in its course by a variety of techniques that may help to clarify this still poorly understood entity.
Many genetically determined cystic kidney disorders occur in children. Presenting manifestations related to the kidney include failure to thrive, abdominal enlargement or flank masses, progressive renal failure, or urinary tract infection. Radiological techniques often yield information helpful in establishing the type and extent of renal lesions. Cataloging the cystic renal disease in terms of genetic patterns, the involvement of liver or another organs, and the nature of the disorder of renal architecture is helpful in establishing the proper handling of affected children, and in genetic counseling.
"Medullary sponge kidney" applies to pathologically dilated collecting tubules within one or more renal pyramids of one or both kidneys, almost always diagnosed radiographically, of uncertain etiology, and presenting a clinical spectrum varying from an asymptomatic, incidental finding to severely complicating calcareous-infective disease, renal insufficiency, and death. Recognition of the characteristic urographic pattern affords the patient presenting clinically with hematuria, ureteral colic, urinary tract infection, or nephrocalcinosis a prompt diagnosis with a frequently benign prognosis, and usually averts more extensive or invasive investigations.
Renal cysts are a heterogeneous group comprising heritable, developmental, and acquired disorders. The classification presented here has been developed, as have several others in the past, to incorporate radiographic, functional, and genetic contributions in its clinicopathologic correlations. Its major categories are as follows: (1) dysplastic cysts arising in kidneys that have undergone abnormal morphogenesis and differentiation; (2) polycystic disease of autosomal recessive and autosomal dominant types; (3) heritable syndromes of multiple malformations with renal cysts resulting from presumed metabolic injury; (4) isolated cortical cysts of unknown pathogenesis; (5) medullary cysts of several types, including medullary sponge kidney and the progressive syndromes of medullary cystic disease, familial juvenile nephronophthisis, and renal-retinal dysplasia; (6) acquired parenchymal cysts of diverse origins; and (7) extraparenchymal cysts. This classification, which has been revised repeatedly over the years, is still tentative and undoubtedly will be revised again.
The great diversity of the various forms of renal cystic disease results in a formidable diagnostic challenge to the roentgenologist and clinician alike. Until recently, adequate diagnosis required surgical exploration or biopsy, or both, to establish benignity or to confirm the suspicion of a more esoteric form of renal cystic disease. Now, however, with refinements in excretory urography with tomography, bolus and infusion nephrotomography, selective renal arteriography, percutaneous aspiration of cysts, and sonography, the accuracy of a clinical diagnosis of cystic disease has approached that of surgical exploration and biopsy. In addition these noninvasive techniques eliminate the morbidity and mortality associated with surgical procedures.
To investigate the role of components of the renin-angiotensin-aldosterone system and plasma progesterone concentrations in the pathophysiology of hypertension in pregnancy, sequential measurements were made throughout pregnancy in 45 normotensive subjects, 41 other pregnant patients in whom hypertension became manifest only during pregnancy and 26 patients with chronic hypertension antedating pregnancy. Among the normotensive subjects plasma renin activity and substrate, plasma aldosterone and progesterone concentrations were elevated as early as the sixth week of gestation. While consistent, progressive, further increases were noted in renin substrate, aldosterone and pregesterone concentrations during pregnancy, plasma renin activity did not continue to rise. In both hypertensive groups, plasma renin activity and aldosterone concentration were significantly suppressed during the last trimester despite levels of renin substrate and progesterone that were not significantly different than those observed in normotensive pregnancy. These observations confirm earlier studies reporting suppression near term of plasma renin activity in toxemia and indicate from these prospective observations that they are secondary effects. These studies, in addition, demonstrate parallel suppression of plasma aldosterone concentration in toxemia. The current report also indicates that this suppression is not due to a decrease in renin substrate concentration and that a hypothesized deficiency of plasma progesterone, which was not observed in the hypertensive subjects, does not play a permissive role in the development of hypertension.
Plasma renin activity, renin substrate, angiotensin II, aldosterone and cortisol were measured concurrently and renin concentration calculated in plasma from mothers during labor and delivery, from cord and from newborn infants. The renin-angiotensin-aldosterone system was found strongly stimulated in both mother and fetus. The high values of plasma renin activity in fetus were due exclusively to the high renin concentrations the substrate concentration being normal. In the mother, however, the markedly elevated renin substrate resulted in a doubling of relative values of renin activity compared to renin concentration. Therefore gradients of renin and renin substrate across the placenta are established, but the resulting renin activity is similar on both sides and the levels of generated angiotensin II are also nearly indentical with a good correlation between these last parameters. Aldosterone is as elevated in mother as in fetus whereas cortisol, due to its binding to transcortin, is twice as high in mother as in fetus. No correlation was found between renin activity or concentration of angiotensin II and aldosterone or cortisol indicating that other factors controlling aldosterone are involved.
Several methods were used in an attempt to produce preeclampsia in the pregnant rat. Desoxycorticosterone acetate plus increased NaCl intake produced hypertension, proteinuria, rapid weight gain, convulsions, decreased litter size, decreased offspring weight, increased fetal and maternal mortality, and renal lesions similar to those seen in human preeclampsia. Injection of placenta in Freund's adjuvant produced mild blood pressure elevation and proteinuria in the pregnant rat. Rabbit antirat placenta serum produced hypertension in the pregnant rat but not in the nonpregnant rat. Liver congestion and renal glomerular congestion were observed in both pregnant and non-pregnant rats. Pregnancy in the rat reduced hypertension produced by applying a Goldblatt clamp prior to breeding. Uterine ischemia produced by wrapping the uterus in cellophane produced mild blood pressure elevation and proteinuria. A vitamin-E-deficient diet that contained substantial amounts of partially perioxidized, polyunsaturated fatty acids produced morphological lesions in the pregnant rat similar to those seen in human preeclampsia, but hypertension, edema, and proteinuria were absent. None of the maneuvers was effective in producing a complete model of human preeclampsia, but they do provide material for study that could answer somebasic questions about preeclampsia.
