Electron microscopy in end stage renal disease: a case of Fabry's disease

Fabry's disease is an X-linked error of metabolism with deficiency of the enzyme α-glycosidase A, and glycosphingolipid accumulation in multiple tissues. Patients may be asymptomatic and present with advanced disease. We report a case of a 38 year old white male who presented with end stage renal disease of unknown etiology. He received a living-related donor kidney transplant (mother), but lost the graft after 10 years to multiple episodes of rejection. Review of the native renal biopsy with added ultrastructural studies established the diagnosis of Fabry's disease. Evaluation of renal biopsies showing advanced chronic injury should include electron microscopic studies, which may reveal characteristic diagnostic features, as seen in this case of Fabry's disease. Identification of hereditary disorders involving the kidney is important for appropriate treatment and prevention of disease recurrence. Potential living related donors should be screened for genetic involvement.     

AN AUTOPSY CASE OF FABRY'S DISEASE**

An autopsy case of a 35-year-old male with Fabry's disease was Investigated histologically, electron microscopically and biochemically. Accumulation of both ceramide-trihexoslde and ceramide-dihexoside in the kidney, lymph nodes, nervous ganglion and spinal cord, as well as deficiency of α-galactosldase in the kidney tissues were found. Electron microscopically the intracellular deposits presented diverse features including those with fingerprint-like ultrastructure in the medullary cord reticulum cells which were alclan blue positive, rod-shaped deposits of the capillary endothelial cells of the lymph nodes and several other types of deposits of the spinal ganglion cells.     

The kidney in Fabry's disease

Fabry disease (FD) is an X‐linked disease in which mutations of the GLA gene result in a deficiency of the enzyme α‐galactosidase A and subsequent progressive, intralysosomal deposition of undegraded glycosphingolipid products, primarily globotriaosylceramide, in multiple organs. Progressive nephropathy is one of the main features of FD and is marked by an insidious development, with an overall rate of progression of chronic kidney disease (CKD) very similar to diabetic nephropathy. Untreated patients usually develop end stage renal disease in their 50s. The decline in renal function in FD is adversely affected by male gender, advanced CKD, hypertension and, in particular, severe proteinuria. Enzyme replacement therapy (ERT) has been shown to slow the progression of Fabry nephropathy. The current consensus is that ERT should be started in all men and women with signs of renal involvement.     

Renal cystic diseases: a review

This review aims to assist in the categorization of inherited, developmental, and acquired cystic disease of the kidney as well as to provide a pertinent, up-to-date bibliography. The conditions included are autosomal-dominant polycystic kidney disease, autosomal-recessive polycystic kidney disease, unilateral renal cystic disease (localized cystic disease), renal simple cysts, multicystic dysplastic kidney, pluricystic kidney of the multiple malformation syndromes, juvenile nephronophthisis and medullary cystic disease, medullary sponge kidney, primary glomerulocystic kidney disease, and glomerulocystic kidney associated with several systemic disorders mainly of genetic or chromosomal etiology, cystic kidney in tuberous sclerosis, and in von Hippel-Lindau syndrome, cystic nephroma, cystic variant of congenital mesoblastic nephroma, mixed epithelial stromal tumor of the kidney, renal lymphangioma, pyelocalyceal cyst, peripylic cyst and perinephric pseudocyst, acquired renal cystic disease of long-term dialysis, and cystic renal cell carcinoma and sarcoma. Whereas the gross and histologic appearance of some of these conditions may be diagnostic, clinical and sometimes molecular studies may be necessary to define other types.     

Angiomyolipome der Nieren bei Morbus Bourneville-Pringle

Summary Three cases with renal angiomyolipoma in Bourneville's disease are reported. In two patients advanced renal insufficiency developed, one being treated by chronic intermittent hemodialysis. In the third patient rupture of angiomyolipoma with severe retroperitoneal bleeding occurred. In one patient, tumorous enlargement initially was diagnosed only in the right kidney and preceded angiomyolipoma of the left kidney for several years. In this patient nephrectomy was performed because malignancy was assumed before diagnosis of Bourneville's disease was established. Occasionally, histology may suggest sarcomatous changes. However, the absence of distant metastasis and the overall long survival of patients with renal angiomyolipoma in Bourneville's disease underline the benign character of the tumor. Treatment should be conservative because surgical intervention with loss of kidney parenchyma may enhance progression to end-stage renal failure.

     

A Case of Hypertrophic Cranial Pachymeningitis Presenting with Scleritis in a Patient with Undifferentiated Connective Tissue Disease

Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been reported to be infrequently associated with systemic autoimmune disorders such as Wegener''s granulomatosis, rheumatoid arthritis, sarcoidosis, Behçet''s disease, Sjögren syndrome, and temporal arteritis. Here, we report a case of HCP initially presented with scleritis and headache in a patient with undifferenciated connective tissue disease (UCTD). HCP was initially suspected on brain magnetic resonance imaging and defined pathologically on meningial biopsy. Immunologic studies showed the presence of anti-RNP antibody. After high dose corticosteroid therapy, the patient''s symptoms and radiologic abnormalities of brain were improved. Our case suggested that HCP should be considered in the differential diagnosis of headache in a patient with UCTD presenting with scleritis.     

An Atypical Ultrastructural Pattern in Fabry's Disease: A Study on Its Nature and Incidence in 7 Cases

This is a report on a stored lipid atypical ultrastructural pattern in skin samples of Fabry's disease expressed exclusively in the endothelium. The pattern consisted of intersecting short crescentic tightly packed membranes with a periodicity identical to that in classical ultrastructural variants. At low magnification the lysosomal aggregates of the material resembled “sunbursts” or aggregates of densely packed squirming villus-like structures. According to results of ultrastructural, lipid, and lectin histochemical analyses including analysis of the patients' blood groups, it could be concluded that it is just a variant physical state of the otherwise typical Fabry lipid. Its origin could be attributed to impeded formation (or maintenance) of larger lipid lamellae. It was found in great amounts in skin capillaries in 2 cases, and rarely in 5 additional cases. Knowledge of this atypical ultrastructural pattern is of practical significance because it could, if prevalent, cause diagnostic problems.     

Generalized Vascular Dissection on Pathological Examination in a Patient With Polycystic Kidney Disease and Acute Aortic Dissection

Polycystic kidney disease (PKD) is a multiple cystic disease involving both the kidneys. Some studies have reported cases of patients with PKD and concurrent aortic dissection; however, autopsy has been performed in only few of these cases. Here, we present the case of a 62-year-old male patient with PKD who showed generalized vascular degeneration, including aortic dissection. The patient had a family history of autosomal dominant PKD and was brought to our hospital because of cardiopulmonary arrest. He was diagnosed with Stanford type A aortic dissection and died on the same day, despite being under cardiopulmonary resuscitation. Autopsy detected multiple cysts in the kidneys, liver, pancreas, and testes. Moreover, multiple tears in the vascular wall of the splenic artery and superior mesenteric artery, including the aorta, were observed. The case findings indicate that patients with PKD may develop associated generalized vascular disease; however, development of cerebral aneurysms and aortic dissections with PKD is particularly serious. Therefore, suitable screening tests must be developed for the early diagnosis and disease characterization, thus, ensuring that the appropriate treatment is administered to the patients.     

Spontaneous abortion, sex ratio and facial cleft malformations

Results of an ongoing prospective study of progeny of patients with adult-onset polycystic kidney disease using grey-scale ultrasound and high-dose nephrotomography are reported. Six asymptomatic subjects out of 17 at risk for polycystic kidney disease were found by ultrasonography to have multiple renal cysts; this included two unrelated children aged 18 months and 6 y who had normal high-dose nephrotomography. We suggest that ultrasonography may be the method of choice for presymptomatic detection of polycystic kidney disease. Serial studies of at-risk individuals by sonography will be useful in determining the earliest age of detection, the latest age of ultrasonography presentation, and in following the natural history of polycystic kidney disease.     

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.     

Targeting apoptosis signal-regulating kinase 1 in acute and chronic kidney disease

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase (MAP3K) family which acts as an upstream regulator for the activation of p38 MAPK and c-Jun N-terminal kinase (JNK). Experimental studies have demonstrated a pathogenic role for p38 MAPK and JNK activation in a number of kidney disease models; however, clinical studies targeting these kinases directly have been problematic due to their role in homeostatic functions. In comparison, ASK1 is activated in pathological states and is not essential for homeostatic functions, suggesting that ASK1 may be a safe and effective therapeutic target to inhibit p38 MAPK and JNK signaling in disease. Animal model studies using Ask1 gene deficient mice or a selective ASK1 inhibitor have demonstrated that ASK1 blockade is effective in a variety of acute and chronic kidney diseases; preventing cell injury, inflammation, fibrosis, albuminuria, and renal function impairment. Positive outcomes from these experimental studies have led to the current evaluation of an ASK1 inhibitor in patients with moderate to advanced diabetic kidney disease. This review summarizes the preclinical studies of ASK1 blockade in models of acute and chronic kidney injury and a clinical study examining ASK1 inhibitor treatment in diabetic kidney disease.     

Unilateral autosomal dominant polycystic kidney disease with contralateral renal agenesis: a case report

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.     

Morphologic Heterogeneity of Renal Light-Chain Deposition Disease

Light-chain deposition disease (LCDD) of the kidney is defined as deposition of monotypic light chains (LC) within glomerular (GBM) and tubular (TBM) basement membranes. The morphologic features of pure renal LCDD have been presented only in case reports or small series. The aim of this study was to perform a comprehensive evaluation of the light (LM), immunofluorescence (IF), and electron microscopic (EM) features of pure renal LCDD in a large series of biopsies. Out of 46 cases assembled, 42 had multiple myeloma, 2 had monoclonal gammopathy of unknown significance, and in 2 patients no lymphoproliferative disease was identified. The most common LM lesion of LCDD, nodular glomerulosclerosis, was present in only 14 (30%) cases. GBM and/or TBM thickening was found in 3 (6%), mild to moderate mesangial matrix increase in 12 (23%), and unremarkable glomeruli and tubules were seen in 15 (32%) cases. Forty-two had IF and 40 (92%) showed characteristic linear LC immunoreactivity (24 kappa, 16 lambda) along GBM and/or TBM. Among 39 cases in which IF and EM was available, 25 (64%) were positive by both. Two (6%) were negative by IF, but had deposits by EM. In 12 (30%) with immunoreactivity to LC (4 kappa, 8 lambda), no deposits were identified ultrastructurally. This study shows heterogeneous LM lesions in pure LCDD cases. LM alone may be suspicious but not diagnostic of LCDD. Immunofluorescence is more sensitive than EM for detection of LC for the definitive diagnosis of LCDD. This study supports the importance of utilizing kappa and lambda stains in the routine IF panel for diagnosis of LCDD.     

Clinical consequences of developmental programming of low nephron number

Nephron number in humans varies up to 13-fold, likely reflecting the impact of multiple factors on kidney development, including inherited body size and ethnicity, as well as maternal health and nutrition, fetal exposure to gestational diabetes or preeclampsia and other environmental factors, which may potentially be modifiable. Such conditions predispose to low or high offspring birth weight, growth restriction or preterm birth, which have all been associated with increased risks of higher blood pressures and/or kidney dysfunction in later life. Low birth weight, preterm birth, and intrauterine growth restriction are associated with reduced nephron numbers. Humans with hypertension and chronic kidney disease tend to have fewer nephrons than their counterparts with normal blood pressures or kidney function. A developmentally programmed reduction in nephron number therefore enhances an individual's susceptibility to hypertension and kidney disease in later life. A low nephron number at birth may not lead to kidney dysfunction alone except when severe, but in the face of superimposed acute or chronic kidney injury, a kidney endowed with fewer nephrons may be less able to adapt, and overt kidney disease may develop. Given that millions of babies are born either too small, too big or too soon each year, the population impact of altered renal programming is likely to be significant. Many gestational exposures are modifiable, therefore urgent attention is required to implement public health measures to optimize maternal, fetal, and child health, to prevent or mitigate the consequences of developmental programming, to improve the health future generations.     

Clinico-pathological profile of 22 cases of cystic renal dysplasia

Renal dysplasia is one of the major renal developmental anomaly characterized by abnormal structural organization and development of metanephric elements. It is usually detected antenatally or in early childhood. The kidney may be multicystic, aplastic, hypoplastic or duplex. We studied 22 cases of cystic renal dysplasia diagnosed over a period often years to identify the spectrum of morphological changes in dysplastic kidney, with special emphasis on mesenchymal changes. Clinical, radiological and gross morphologicalfeatures were noted. Microscopic features were studied in detail, including the epithelial and mesenchymal changes. Twenty-one of the 22 cases studied were children. One case was a 21-year-old adult, which is a rare age at presentation. Male to female ratio was 1.1:1. One of our patients had contra-lateral ureteric stenosis, a rare anomaly reported with renal dysplasia. Ten patients, all autopsy cases, had multi-system congenital anomalies. As cystic renal dysplasia is not a hereditary disease, it must be differentiated from polycystic kidney disease. Other differential diagnoses are cystic nephroma and cystic partially differentiated nephroblastoma. Histopathological examination is the final diagnostic tool since radiological features alone may not be sufficient to exclude other cystic renal lesions. Cartilage may not be seen in all cases of renal dysplasia. Once diagnosed, other associated anomalies should also be looked for.     

Disease Stage Characterization of Hepatorenal Fibrocystic Pathology in the PCK Rat Model of ARPKD

The rat Pck gene is orthologous to the human PKHD1 gene responsible for autosomal recessive polycystic kidney disease (ARPKD). Both renal and hepatic fibrocystic pathology occur in ARPKD. Affected humans have a variable rate of progression, from morbidly affected infants to those surviving into adulthood. This study evaluated the PCK rat, a model of slowly progressive ARPKD. This model originated in Japan and was rederived to be offered commercially by Charles River Laboratories (Wilmington, MA). Previous studies have described the basic aspects of PCK pathology from privately held colonies. This study provides a comprehensive characterization of rats from those commercially available. Rats were bred, maintained on a 12:12 hr light/dark cycle, fed (7002 Teklad), and water provided ad libitum. Male and female rats were evaluated from 4 through 35 weeks of age with histology and serum chemistry. As the hepatorenal fibrocystic disease progressed beyond 18 weeks, the renal pathology (kidney weight, total cyst volume) and renal dysfunction (BUN and serum creatinine) tended to be more severe in males, whereas liver pathology (liver weight as % of body weight and hepatic fibrocystic volume) tended to be more severe in females. Hyperlipidemia was evident in both genders after 18 weeks. Bile secretion was increased in PCK rats compared with age‐matched Sprague Dawley rats. The PCK is an increasingly used orthologous rodent model of human ARPKD. This characterization study of hepatorenal fibrocystic pathology in PCK rats should help researchers select stages of pathology to study and/or monitor disease progression during their longitudinal studies. Anat Rec 293:1279–1288, 2010. © 2010 Wiley‐Liss, Inc.     

Common Impact of Chronic Kidney Disease and Brain Microhemorrhages on Cerebral Aβ Pathology in SHRSP

While chronic kidney disease seems to be an independent risk factor for cognitive decline, its impact on cerebral amyloid‐β (Aβ) depositions, one hallmark of Alzheimer's Disease (AD) pathology, has not been investigated. Utilizing 80 male nontransgenic spontaneously hypertensive stroke prone rats (SHRSP) at various ages (12 to 44 weeks), tubulointerstitial renal damage, prevalence of cerebral microhemorrhages and Aβ accumulations were quantified. Using age‐adjusted general linear models we investigated the main and interaction effects of renal damage and cerebral microhemorrhages on cerebral Aβ load. In addition, using post mortem human brain tissue of 16 stroke patients we examined the co‐localization of perivascular Aβ deposits and small vessel wall damage. Statistical models revealed an age‐independent main effect of tubulointerstitial kidney damage on brain Aβ accumulations, which was reinforced by the consecutive presence of cerebral microhemorrhages. Moreover, cerebral microhemorrhages independently predicted brain Aβ burden in SHRSP. In up to 69% of all human cases perivascular Aβ deposits were detected in the direct vicinity of small vessel wall damage. Our results support the associations between vascular pathology and Aβ deposition, and demonstrate a relationship between chronic kidney disease and cerebral Aβ pathology. Hence, our data suggest that prevention of chronic renal damage may reduce cerebral Aβ pathology.     

The cardiorenal link in advanced cirrhosis

A considerable number of patients with advanced cirrhosis develop a hepatorenal syndrome. The pathogenesis involves liver dysfunction, splanchnic vasodilatation, and activation of vasoconstrictive systems. There are now several observations that indicate a relation between the renal failure and impaired cardiac function in patients with advanced cirrhosis. Cirrhotic cardiomyopathy has been described as a condition with impaired contractile responsiveness to stress and altered diastolic relaxation. We propose a cardiorenal interaction in patients with advanced cirrhosis and renal dysfunction that refers to a condition where cardiac dysfunction in cirrhosis is a major determinant of kidney function and survival. Thus, the relation between cardiac dysfunction and renal insufficiency should be target for future studies and development of new treatments should focus on ameliorating the cardiac dysfunction.     

Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report

Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient''s renal function was markedly improved after short-term treatment with high-dose steroid.

Graphical Abstract

相似文献