Search

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.

Hypertension and proteinuria were observed in a 2-year-old child with type IA (von Gierke's) glycogen storage disease (GSD). She had evidence of hyperfiltration and had elevated selective renal vein renins. On renal biopsy, increased mesangial cell matrix and cellularity were observed with focal thickening and irregularity of the basement membrane. This case may be representative of the early renal findings in type IA GSD.

Amyloidosis may present with involvement of a variety of organ systems. Cutaneous involvement is a relatively common finding in patients with systemic amyloidosis. The occurrence of bullous skin lesions, however, is rare; only a few such cases have been previously reported. We describe a patient who presented with a subepidermal bullous skin disease initially thought to be bullous pemphigoid based on both clinical and histologic appearances. The patient subsequently developed the nephrotic syndrome. Biopsy specimens of the skin and kidney showed involvement of both organs with amyloid, and amyloid was later found in the spleen, heart, and nervous system. No subsequent evidence of myeloma was found in this patient. The clinical, histopathologic, immunofluorescent, and electron microscopic findings of systemic amyloidosis are discussed.

The patholophysiologic significance of vascular congestion in the mechanism of ischemic acute renal failure following postocclusive reflow was studied with a novel hemorheologic probe, pentoxifylline. Using the autoperfused rat kidney model, inulin clearances (CIN), urine flow rates (UFR), renal electrolyte excretions, and renal hemodynamic parameters (RVR, RBP, RBF) were compared in saline- and pentoxifylline-treated anesthetized rats prior to and following a 45-min occlusive period. Renal functional and hemodynamic parameters were significantly altered in saline controls. In contrast, postischemia treatment with pentoxifylline was associated with significant recovery in CIN and UFR, and stable RVR, RBF, and RBP. Kidneys treated with saline infusion had pronounced vascular congestion, in contrast to those administered pentoxifylline. Coupled with the absence in medullary hyperemia, the present experiments support the role of vascular congestion in ischemic acute renal failure. Pentoxifylline, administered in pharmacologic doses after the insult, provided benefit during the initiation phase of postischemic acute renal failure. These data strengthen the opinion that ischemic insult results in vascular congestion, and that restoration of blood flow will prevent further deterioration in renal function.

The impact of synthetic atrial natriuretic peptide (sANP) on renal function following cold ischemic injury was studied in a canine autotransplant model. Following a prenephrectomy inulin clearance determination (CIn), the left kidney was excised, flushed with Eurocollins solution, and cold-stored for 24 hours. Immediately following reperfusion and a 10 minute equilibration period, baseline CIn was measured over a 20-minute time interval (Collection Period I). Experimental animals (N = 11) then received 1 mcg/kg sANP by intravenous bolus followed by a continuous infusion at 0.3 mcg/kg/min for 30 minutes. CIn was measured throughout the infusion (Collection Period II). Normal saline was substituted for sANP in control animals (N = 11). CIn was also measured 24 hours following reimplantation in seven control and seven sANP-treated animals. Autograft inulin clearance increased from 0.32 +/- 0.11 ml/min during Period I to 2.5 +/- 0.6 ml/min during sANP infusion (P less than 0.01). This increase in CIn associated with ANP infusion was accompanied by increases in urine flow rate (V) (0.15 +/- 0.05 ml/min to 0.98 +/- 0.21 ml/min, P less than 0.01) and renal blood flow (RBF) measured by electromagnetic flow probe (85 +/- 17 ml/min to 171 +/- 13 ml/min, P less than 0.05). No significant changes in CIn, V, or RBF occurred in control animals between periods I and II. Although systemic blood pressure declined during sANP infusion, it did not decrease to an extent that compromised peripheral perfusion. CIn determined 24 hours after autograft reimplantation in the ANP-treated animals approximated or exceeded values determined during ANP infusion (Period II).(ABSTRACT TRUNCATED AT 250 WORDS)

A case of paravertebral extramedullary hematopoiesis in a patient with sickle-cell anemia-beta-thalassemia is reported. Interesting aspects in this case, including the high level of Hb F and large number of nucleated erythrocytes in the peripheral blood, are discussed. Fifty-five cases of intrathoracic extramedullary hematopoiesis have been reported. Most of these cases occurred in patients with thalassemia or hereditary spherocytosis. Extramedullary hematopoiesis should be considered in the differential diagnosis of a posterior mediastinal mass in a patient who has chronic anemia or other syndromes associated with extramedullary hematopoiesis.

We present a case of acquired renal cystic disease in a patient with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus who was dialysis dependent for 5 years. Renal hemorrhage and neoplastic transformation of the cyst epithelium are the two major complications of acquired renal cystic disease, and were present in this patient. The full clinical significance of the acquired renal cystic lesion is still unclear, although the possibility of renal tumors and massive renal and retroperitoneal hemorrhage should be considered in the long-term dialysis population.

Male Fischer rats received daily intraperitoneal injections of cyclosporine (IV preparation containing CsA + cremophor) diluted in NaCl or in NaCl + cremophor. At the dose of 100 mg and 50 mg/kg/day the animals developed seizures, motor weakness and died at 4-7 days. Light microscopy at 7 days in these rats showed diffuse vacuolization of all segments of the proximal tubules which was very extensive in the outer stripe. At the dose of 25 mg and 15 mg/kg/day animals were free of symptoms and were sacrificed at day 15 for functional and histological studies. Light and electron microscopy showed cytoplasmic vacuolization in all segments of the proximal tubules. Crystal structures were observed in the experimental animals as well as in the control group that received cremophor + NaCl. The CsA blood levels were at the range of 134-236 ng/ml. Reduction of the glomerular filtration rate was observed in experimental animals as compared with the controls. We concluded that CsA is not the cause of an interstitial nephritis in the Fischer rats and that CsA is nephrotoxic to all segments of the proximal tubules. The cremophor is the cause of the crystal structures seen in the proximal tubules.

The renal pelvis of the rat is characterized by extensions called specialized fornices that penetrate into the outer zone of the outer medulla (a type II as classified by Pfeiffer, 1968, 1970). The renal pelvic epithelium, therefore, covers areas of the kidney from the inner medulla, the inner and outer stripe of the outer medulla, and the cortex. The renal pelves of seven rats were studied by transmission and scanning electron microscopy. The transitional epithelium on the nonparenchymal surface of the pelvis was three to four cell layers thick (zone 0-1). This epithelium became thinner where it covered the renal cortex (zone 1-2) or the outer medulla. Although the apical cells of the epithelium retained the asymmetric luminal unit-membrane plaques, the number of cytoplasmic fusiform vesicles decreased as one studied the epithelium progressing over the zones from cortex toward papilla. Scanning electron microscopy demonstrated a small number of surface cells of a different morphology that were characterized by apical microvilli. The number of these microvillous lining cells increased as the epithelium covering the outer (zone 2-3) and inner (zone 3-4) stripe regions of the outer medulla was viewed, until the inner medulla was entirely covered by this cell type. In a reciprocal manner, the cells with the asymmetric apical plaques decreased in numbers and in their morphologic specialization in each successive region. The epithelium surrounding the inner medulla (zone 6-7) was completely devoid of this transitional cell type. Judging from the morphologic characteristics of the epithelia, one could surmise that little exchange of urea, water, and salts would occur with the extrarenal connective tissue or the cortical parenchyma. Recycling of urea might become more important physiologically with the outer stripe parenchyma, and even more so with the increased surfaces of the inner stripe parenchyma that lined the secondary pyramid, as well as with the epithelium lining the medulla.

A malignant fibrous histiocytoma (MFH) arising in the lungs of a 51-year-old man was studied by light and electron microscopy. Features observed were identical to those of MFHs which occur in the skin and subcutaneous tissue and less commonly in other deep locations. By light microscopy, a storiform pattern with admixture of fibroblasts and histiocytes, as well as xanthomatous and giant cells, was noted. Undifferentiated tumor cells along with fibroblasts and histiocytes in different degrees of differentiation were identified ultrastructurally. These findings lend support to the concept that MFH is a sarcoma of primitive mesenchymal cell origin. The addition of the lung as another primary site for the development of this tumor is consistent with the view that MFHs may potentially arise in any part of the body.

Three children had renal histopathologic findings indicative of glycogen storage disease type I. Glomerular basement membrane (GBM) alterations were present in the three patients, particularly so in the two patients with proteinuria. Thickening, lamellation, and glycogen deposition were the characteristic alterations in the GBM. Glomerulosclerosis was prominent in one patient. We suggest that the GBM alteration is related to the glomerular sclerosis and that both are related to metabolic derangements of glycogen storage disease type I.

Cyclosporine (CsA), a powerful immunosuppressive agent that increases graft survival in renal transplant recipients, is often nephrotoxic. The clinical distinction between acute rejection and CsA nephrotoxicity (NT) is a common challenge in the management of these patients. To seek a histologic distinction between acute rejection and CsA-NT, we reviewed the renal biopsies performed prior to initiation of therapy for rejection or nephrotoxicity in two groups of patients. Group 1 (ten patients) had criteria consistent with acute rejection and responded to steroid pulse therapy. Group 2 (15 patients) was treated for CsA-NT and responded to a decrease in the dose of CsA. We conclude that CsA-NT has no specific histologic features. A prominent interstitial mononuclear cell infiltrate as well as tubulitis are features of acute cellular rejection. These findings do not exclude the possibility that rejection and CsA-NT can co-exist in the same patient.

Storage of glutamyl ribose-5-phosphate was identified at autopsy in the brain and kidney of an 8-year-old male who had presented clinically with progressive renal failure and neurological deterioration. In a renal biopsy during life, glomeruli were focally sclerotic and contained foam cells. By electron microscopy, lysosomal accumulation was present in renal tubular and glomerular epithelial cells, hepatic Kupffer cells, and conjunctival connective tissue cells. Ganglion cells in the brain stem had swollen, PAS-positive cytoplasm with central chromatolysis. The cerebral cortex was atrophic and there was loss of Purkinje cells in the cerebellum. The identification of storage was based on biochemical isolation of the compound from the tissues at autopsy. The enzyme deficiency responsible for the storage has not yet been identified.

We report a case in a 38-year-old white woman of a benign primary intratracheal neurilemoma that recurred 12 years after an initial endoscopic excision. Of the 12 intratracheal neurilemomas that have previously been reported, all occurred in white persons in an age range of 6 to 71 years and most were located in the lower trachea and produced symptoms of cough and wheezing.

The glomerular ultrastructure was retrospectively reviewed from 45 renal transplant biopsies with the clinical and light microscopic diagnosis of acute rejection (25 cases) and chronic rejection (20 cases). Three grades of morphologic alteration were ultrastructurally defined. In acute rejection, capillary lumenal obliteration with endothelial cell hypertrophy and cellular infiltration were interpreted as the local glomerular expression of the endothelial vascular alterations of acute humoral rejection and were correlated with a poor graft survival. Graft nephrectomy was necessary in 9 of 11 patients with grade III glomerulopathy. In chronic rejection, thickened basement membranes and increased amount of mesangial matrix were considered the result of ischemia. The degree of ultrastructural glomerular alterations in chronic rejection did not correlate with graft survival. Urine protein values were consistently elevated, although poorly correlated with the severity of glomerular alterations. Recurrent glomerulonephritis was not documented in any case. We concluded that the glomerular alteration in acute rejection is a component of acute humoral rejection and that the degree of glomerulopathy in acute rejection is a good predictor of the graft survival.

We studied the kidneys from ten patients with adult (autosomal dominant) polycystic kidney disease (APKD) stained with lectins specific for different segments of the nephron on 20 cysts from each case (ranging in size from 0.1 to 1.3 cm in nine cases and from 1.5 to 6 cm in one case). The epithelium of all cysts with positive reactivity (Arachis hypogaea and epithelial membrane antigen) was of collecting duct origin. Many cysts remained unstained. Cysts of proximal tubule origin could not be identified using the specific lectin Lotus tetragonolobus. Focal epithelial hyperplasia appeared in the collecting duct cysts. Cysts surrounded by smooth muscle were frequent and considered to be of collecting duct origin. One case had glomerular cysts. We conclude that the cysts of APKD are principally of collecting duct origin.

Renal failure due to mitomycin chemotherapy is a poorly appreciated entity often associated with microangiopathic hemolytic anemia. We describe a 45-year-old man in whom renal failure and anemia developed, without evidence of hemolysis, five months after beginning chemotherapy with mitomycin, fluorouracil, and doxorubicin hydrochloride. A biopsy specimen taken from the patient's kidney showed fibrin thrombi in two of 18 glomeruli and in several small arteries. The patient's condition required institution of maintenance dialysis. Similar reports from the literature are reviewed.

Acute oliguric renal failure associated with bacterial pyelonephritis is a rarely recognized clinical entity. We report a woman with an ectopic pregnancy who developed acute renal failure requiring dialytic support. The renal biopsy revealed focal microabscess formation and leukocyte interstitial infiltration compatible with suppurative pyelonephritis. Although her renal function improved gradually with antimicrobial treatment, the process was incomplete and renal dysfunction persisted at a 10-week follow-up, suggesting permanent renal damage.