Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease

Proliferation of renal tubular epithelial cells is considered a major factor leading to cyst formation in human polycystic kidney disease (PKD). The Han:SPRD rat model for inherited PKD permits a close scrutiny, especially for early stages of the disease, and shows numerous similarities to human autosomal dominant PKD (ADPKD). In this study, the exact in vivo proliferation rate in Han:SPRD rat kidneys was evaluated in a cell type-specific manner, using immunohistochemistry with antibody to proliferating cell nuclear antigen (PCNA). The proliferation index (PI; percentage of PCNA-positive cell nuclei) was determined in normal and cystically altered tissue, and a relationship between proliferative activity and alterations in extracellular matrix expression was established using in situ hybridization for collagen I and IV mRNA. Heterozygously affected rats (cy/+) showed strong increases of PI values in cystically altered nephron portions that were mostly derived from proximal tubule. Cell proliferation obviously preceded cyst formation, because early in the progression of the disease, the normal-appearing tubules from PKD kidneys had markedly increased PI values compared with healthy controls (14.1-fold in 3-mo-old rats and 11.9-fold in 12-mo-old rats; P < 0.05), whereas later stages revealed a more generalized cystic degeneration of the nephron, with increases in PI between 14- and 82-fold, depending on the respective category of cystic epithelia. In cysts with a distal phenotype, changes were less pronounced. No significant differences were encountered between the two age groups. Proliferation was also present in interstitial cells, whereas glomeruli were unchanged. Increases in epithelial and interstitial proliferation coincided with an overexpression of matrix compounds. For comparison, changes in homozygously affected rats (cy/cy) showed up to several hundred-fold elevated PI values. These results indicate that in the Han:SPRD model for ADPKD, cystic malformation of the nephron is preceded by and coincides with enhanced epithelial and interstitial cell proliferation. Altered cell-matrix interactions seem to be directly involved in the disruption of epithelial differentiation.     

Morphology of cystic renal lesions. Lectin and immuno-histochemical study

Renal cystic disease include heritable, developmental and acquired disorders. Morphological features were extensively studied mainly in cases of autosomal dominant polycystic and experimentally induced cystic disorders. We report the immunohistochemical (cytokeratin, epithelial membrane antigen, vimentin, Tamm-Horsfall protein, proliferating cell nuclear antigen) and lectin-binding (soybean agglutinin, Dolichos biflorus agglutinin) profile of cystic kidneys from 9 surgically removed and 21 autopsy cases. The primary renal diseases displayed great diversity. Beside polycystic kidney diseases we studied cysts associated to renal neoplasm, hemodialysis, nephrosis syndrome and chronic transplant rejection. Cystic epithelium demonstrated positive reactions with distal tubular markers (epithelial membrane antigen, cytokeratin) or collecting duct (soybean agglutinin, Dolichos biflorus agglutinin) and Henle loop markers (Tamm-Horsfall protein) but the latter in lesser extent. The large number of the vimentin positive cases are suggestive to dedifferentiation or cellular regeneration. The former might be underlined by the diffuse cytoplasmic or basolateral membrane staining of the epithelial membrane antigen in some cystic epithelial cells. Not the cystic epithelium but rather the neighbouring non-dilated tubular cells and interstitial cells presented proliferative activity which was most intense in areas where vimentin and variable nephron segment markers in the same tissue were expressed. Positive reaction of the type IV basement membrane collagen and the rate of the inflammation failed to show similar connection. This finding suggests the importance of the inflammatory cells in the development and/or expansion of the cysts.     

Evaluation of apoptosis and cell proliferation in experimentally induced renal cysts

Cell proliferation and apoptosis in renal cysts induced by streptozotocin, alloxan and ferric-nitrilotriacetate were investigated in rats. In the kidneys of all treated animals dilated tubules at the cortico-medullary region, large cysts, glomerular cysts and tubular dilation in the medullary area were found. Both cell proliferation and apoptosis were increased in the epithelium of the non-dilated tubules, in the mesangial and interstitial cells. Cells lining the dilated tubules or cysts demonstrated apoptosis but their proliferating activity was low. By calculating the proliferation-apoptosis ratio we found that alloxan did not change the balance between the two mechanisms. Meanwhile streptozotocin resulted in an increased apoptosis and ferric-nitrilotriacetate in an increased cell proliferation. p53 expression might be responsible for the uncontrolled proliferation in rats treated with ferric-nitrilotriacetate as this oncoprotein was diffusely present in tubular cell nuclei. The observed apoptosis seemed to be independent of bcl-2 oncoprotein expression. We assume that the initial factor in such cystogenesis should be a cellular injury due to direct toxic or to the diabetogenic effect of the drugs. The latter is more likely as all the animals were hyperglycemic and insulin treatment following administration of streptozotocin prevented the morphologic changes.     

Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers

Evidence from in vitro studies indicates that increased proliferation of epithelial cells and secretion of fluid by these cells may be important factors in the progressive enlargement of renal cysts. The rate of cellular proliferation and fluid secretion by cyst epithelium in vitro can be strikingly accelerated by cyclic adenosine 3'5' monophosphate (cAMP) and agonists that lead to the production of this nucleotide. The extent to which renal cAMP content is increased in polycystic kidneys is unknown. In the current study, we determined the amount of this nucleotide in intact kidneys, cyst fluid, plasma, and urine in nonazotemic mice (DBA/2FG-pcy/pcy) with a slowly progressive form of inherited polycystic kidney disease (PKD). In 45 pcy/pcy mice studied 20, 45, or 70 days after birth, the total kidney cAMP content was 0.22 +/- 0.01, 0.46 +/- 0.02, and 0.90 +/- 0.05 pmol/mg tissue, respectively. By contrast, in 37 control DBA/2J mice the levels of cAMP at identical times remained relatively constant at 0.22 +/- 0.01, 0.21 +/- 0.01, and 0.29 +/- 0.01 pmol/mg tissue, respectively. In 70-day-old nonazotemic pcy/pcy mice with normal serum levels of parathyroid hormone, cAMP generated by the kidneys (nephrogenous cAMP) was 22.9 +/- 2.8 nmol/100 mL creatinine clearance, compared with 6.5 +/- 1.3 in normal animals of the same age (P < 0.001). The cyst fluids of 70-day-old pcy/pcy mice contained a lipid that increased transepithelial secretion of fluid by MDCK monolayers from a baseline of 0.012 +/- 0.002 to 0.136 +/- 0.008 microL/cm2/hr (P < 0.05). This lipid also stimulated cellular proliferation by monolayers of cultured MDCK and LLC-PK1 cells 2.5- and 7.9-fold (P < .05), respectively, and stimulated cAMP accumulation by these cells 1.6- and 2.0-fold (P < .05), respectively. These studies illustrate that renal cAMP production and excretion increase in concert with the cystic enlargement of the kidneys in DBA/2FG-pcy/pcy mice and identify a lipid cAMP agonist in murine renal cystic kidney disease.     

Transfection of C6 glioma cells with the bax gene and increased sensitivity to treatment with cytosine arabinoside

BACKGROUND: Prolonged dialysis is associated with acquired cystic kidney disease (ACKD) and also higher incidence of renal cell carcinoma. Relationship among dialysis, tubular cell proliferation, development of cystic change and neoplastic transformation is not clearly known. Whether dialysis causes additional stress on tubular cells is also conjectural. Study of heat shock protein (HSP) expression which are rapidly synthesized in cells in response to a variety of stresses may be helpful in this regard. METHODS: To evaluate dialysis induced early changes in end stage renal disease (ESRD), kidneys from eight adult autopsied patients were examined (group I) who were on weekly maintenance haemodialysis for 3-12 months. The heat shock protein (HSP 72/73) expression of tubular epithelial cells and their proliferating cell nuclear antigen (PCNA) labelling index (LI) were studied by immunohistochemistry using monoclonal antibodies. For comparison similar study was carried out in 10 cases of ESRD (Group II) of similar age and sex distribution who were not dialysed. The atrophic tubules were subtyped morphologically into (1) classic, (2) thyroid, (3) endocrine and (4) super tubules. RESULTS: In the dialysed group (I) the percentage of hyperplastic super tubules (10.6 +/- 4.1%) was significantly higher than in the non-dialysed group (II) (5.2 +/- 1.3%) with a higher PCNA LI (6.8 +/- 2.04%) (group II 4.9 +/- 1.9%) (P < 0.01 to < 0.001). Though grossly not detected, but microscopic cysts and microadenoma like areas were seen in all the cases in group I with a mean diameter of 522.66 +/- 315.25 microns and 494.85 +/- 262.46 microns respectively. They were seen in one case of group II. PCNA LI of the cells in microadenoma (7.2 +/- 3.1%) and microcysts (6.6 +/- 2.6%) were similar to that of super tubules in group I. Quantitation of HSP expression by image analysis (optical density 2.309 +/- 0.155) showed a positive correlation (r = 0.7555) (P < 0.001) with PCNA LI in super tubules indicating a higher induction in the dialysed group. CONCLUSIONS: This study suggests that haemodialysis may cause injury to tubular cells and aggravate stress on an already compromised situation of ESRD leading to increased cell proliferation and more hyperplastic supertubule formation which may be the forerunner of cyst formation as well as neoplastic transformation.     

Treatment of pre-invasive conditions during opportunistic screening and its effectiveness on cervical cancer incidence in one Norwegian county

OBJECTIVE: To identify a correlation between dialysis treatment duration and severity of acquired cystic disease of the end-stage kidney measured by cyst sizes; and assess its effect on spontaneous improvement of anemia. MATERIALS AND METHODS: Ten patients, 6 males and 4 females were selected, who have been on hemodialytic treatment for more than 5 years. There was no patient selected with autosomal dominant polycystic kidney disease. The renal evaluation has been made through ultrasonographic studies. Acquired cystic disease of the end-stage kidney was characterized by finding four or more cysts in both kidneys. The largest cysts were measured for correlation effect. The diagnosis of anemia was established by hematocrit and hemoglobin serum values. It has also been analyzed serum urea, creatinine, albumin, iron, total iron-binding capacity and the per cent saturation of serum transferrin were tested. RESULTS: The patients were properly dialysed (serum urea and creatinine = 98.7 +/- 35 mg/dL e 9.7 +/- 2.7 mg/dL, respectively). There were in good nutritional shape (serum albumin = 4.5 +/- 0.5 g/dL) and had normal serum iron level (serum iron = 80 +/- 34 mg/dL). The prevalence of acquired renal cystic disease was 80%. No finding of malignancy has been detected in these cysts. There was a significant correlation between time on dialysis treatment and hematocrit values (R = 0.70; p < 0.05). Cyst sizes had a direct and significant correlation with hematocrit levels (R = 0.74; p < 0.05). CONCLUSION: These results show that spontaneous improvement on anemia seen in patients on chronic dialysis has a significant correlation with the severity of acquired cystic disease of the end-stage kidney. Our data suggest a functional role of acquired kidney cysts on endogenous erythropoietin production.     

Polycystic kidney and liver disease in cats

This paper reviews 27 cases of polycystic disease of the kidneys and/or liver in cats. The multiple cysts in the kidneys were rounded in all but one case, as described in adult polycystic kidney disease in humans. In 68% of the cats presented with polycystic kidneys, there were also cystic changes of the liver (uni- or multilocular cysts and/or congenital hepatic fibrosis (CHF)). In 1 cat polycystic changes of kidneys and liver were accompanied by cysts in the pancreas. In 5 cases there was severe pancreas fibrosis. Twenty-one of the 27 cats were Persian or Persian-crossbred.     

Animal models of polycystic kidney disease

Polycystic kidney disease (PKD) is one of the most prevalent causes of heritable renal failure. The disease is characterized by the occurrence of numerous fluid-filled cysts within the parenchyma of kidney. The cysts are epithelial in origin and expand in size, leading to crowding of normal kidney tissue. Ultimately, there is gross enlargement of the kidneys with loss of normal functions, and death usually occurs because of complications related to renal failure. Animal models of polycystic kidney disease are proving to be extremely useful for studying the molecular basis of renal cyst formation and for the isolation of genes carrying the mutations. This article describes the various animal models of polycystic kidney disease, spontaneously and experimentally derived, that have recently been identified.     

Immunolocalization of ion transport proteins in human autosomal dominant polycystic kidney epithelial cells

The kidneys of patients with autosomal dominant polycystic kidney disease become massively enlarged due to the progressive expansion of myriad fluid-filled cysts. The epithelial cells that line the cyst walls are responsible for secreting the cyst fluid, but the mechanism through which this secretion occurs is not well established. Recent studies suggest that renal cyst epithelial cells actively secrete Cl across their apical membranes, which in turn drives the transepithelial movement of Na and water. The characteristics of this secretory flux suggest that it is dependent upon the participation of an apical cystic fibrosis transmembrane conductance regulator (CFTR)-like Cl channel and basolateral Na,K-ATPase. To test this hypothesis, we have immunolocalized the CFTR and Na,K-ATPase proteins in intact cysts and in cyst epithelial cells cultured in vitro on permeable filter supports. In both settings, cyst epithelial cells were found to possess Na,K-ATPase exclusively at their basolateral surfaces; apical labeling was not detected. The CFTR protein was present at the apical surfaces of cyst epithelial cells that had been stimulated to secrete through incubation in forskolin. CFTR was detected in intracellular structures in cultured cyst epithelial cells that had not received the forskolin treatment. These results demonstrate that the renal epithelial cells that line cysts in autosomal dominant polycystic kidney disease express transport systems with the appropriate polarity to mediate active Cl and fluid secretion.     

Peroxynitrite formation and apoptosis in transgenic sickle cell mouse kidneys

BACKGROUND: In a previous study, nitric oxide synthases (NOS) were found to be strongly expressed in the tubular epithelium of kidneys of a transgenic mouse model of sickle cell disease (alphaHbetaS[betaMDD]). Because NOS activity is often associated with peroxynitrite formation when superoxide radical (.O-2) is present in abundance, we examined the kidneys of sickle cell mice for nitrotyrosine, considered to be a footprint of ONOO-. METHODS: Western blot and immunohistochemistry for nitrotyrosine was carried out. Since peroxynitrite and other reactive oxygen radicals are capable of causing apoptosis, we also performed agarose gel electrophoresis of kidney DNA and TUNEL staining of nuclei, indicators of apoptosis. RESULTS: Nitration of tyrosine residues of three proteins (kD 66, 57 and 22) was found on Western blot of kidney protein extracts of the sickle cell mice. The degree of tyrosine nitration of the 66 kD protein was not significantly different in the control versus transgenic mice, whereas tyrosine nitration of the 57 and 22 kD proteins was clearly increased in transgenic mice. Strong immunostaining for nitrotyrosine was seen in tubular epithelial cells of the sickle cell mice, in close proximity to positive immunostaining of iNOS. Neither iNOS nor nitrotyrosine was expressed in the control mice. DNA "laddering" was found localized to the same zones of the kidney as nitrotyrosine and iNOS immunostaining. TUNEL assay on mouse kidney tissue sections showed minimal tubular cell apoptosis in normal mouse with hypoxia, mild tubular cell apoptosis in sickle cell mouse in room air, and moderate tubular cell apoptosis in sickle cell mouse with hypoxia. CONCLUSIONS: The observations suggest that ONOO- and perhaps other reactive oxygen species are being produced in the sickle cell kidney. The mechanism may be ischemia/reperfusion due to intermittent vascular occlusion by sickle cells. The resulting hypoxia could result in iNOS activation, superoxide radical and peroxynitrite formation. Two consequences of these reactions appear to be nitration of tyrosine residues of some renal proteins and enhanced apoptosis.     

Cystic kidney diseases

Among all inherited cystic kidney diseases, the commonest are polycystic kidney diseases, which include 2 diseases characterized by their pathological characteristics and their mode of inheritance, namely autosomal dominant or recessive. Autosomal dominant polycystic kidney disease is usually diagnosed in adulthood and is related at least to 2 different genes; PKD1 gene on chromosome 16 accounts for 85% of cases. This frequent disease (1 in 1,000 people) leads to end-stage renal failure in most patients at a mean age of 55 years. Renal ultrasonography allows its detection at an early stage, during childhood or adolescence, and even in utero in some cases. Autosomal recessive polycystic kidney disease, related to a single gene mapped to chromosome 6, is a rare disease, usually diagnosed during infancy because of enlarged kidneys and hypertension. The early occurrence of advanced renal failure is uncommon and only 1/3 of patients require renal replacement therapy during childhood. The term "polycystic kidney disease" should be limited to these 2 diseases; however there are many other inherited conditions including renal cysts like tuberous sclerosis or Hippel-Lindau's disease in adults, and several malformative syndromes in children.     

Cellular apoptosis and proliferation in experimental renal fibrosis

BACKGROUND: The progression of chronic renal failure (CRF) is associated with the progressive deletion of renal cells along with the fibrosis of the kidney. We have studied the role of programmed cell death (apoptosis) in the progression of experimental CRF and renal scarring. METHODS: The sub-total (5/6th) nephrectomy (SNx) model of CRF was studied in adult male Wistar rats, with renal tissue collected from experimental and control animals on days 7, 15, 30, 60, 90, and 120 post SNx (n = 6 per group). These were examined for morphological signs of apoptosis by light and electron microscopy. Further, we stained the nuclear chromatin by the acridine orange fluorescent method and detected signs of DNA cleavage by endonucleases via the principal of TUNEL staining (ApopTag). Rates of cellular proliferation were measured simultaneously by immunohistochemical staining for the proliferating cell nuclear antigen (PCNA). In addition, cell division was monitored by counting of morphologically mitotic motifs detectable by light microscopy. RESULTS: Progressive renal insufficiency associated with glomerulosclerosis and tubulointerstitial fibrosis took place in the majority of SNx rats. In these animals, we noted a marked and progressive increase in the number of apoptotic glomerular, tubular as well as interstitial cells. The most significant apoptotic changes were seen in the tubules of remnant kidneys peaking at day 120 post-SNx. At this stage, the increase in apoptosis compared to controls was 10.33+/-2.67 (M+/-SEM) fold for glomerular cells (P< or =0.006), 26.20+/-4.56 fold for tubular cells (P < 0.0001) and 4.66+/-0.81 fold for interstitial cells (P< or =0.001). Parallel changes in the number of PCNA positive renal cells were observed. Maximal PCNA staining was seen at day 120 when the increase with respect to controls was 14.00+/-4.93 fold (P< or = 0.05) for glomerular cells, 60.01+/-12.20 fold (P< or =0.05) for tubular cells and 28.59+/-4.45 fold (P< or = 0.05) for interstitial cells. As expected, the number of cells undergoing division and detectable by conventional light microscopy was lower at any time point to those expressing PCNA. We also observed a close correlation between the severity of tubular atrophy and tubulointerstitial fibrosis with the rate of tubular apoptosis (r=0.970, R2 =0.941, P< or =0.001). CONCLUSIONS: We have shown a time-dependent increase in apoptosis and PCNA antigen positive staining in the sub-total nephrectomy model of chronic renal failure correlating with the progression of renal fibrosis. PCNA staining did not match analysis for mitosis and was considered to overestimate the number of proliferating cells in the tissue. With this reservation in mind and taking into account the relative time-frames in vivo of apoptosis and proliferation; apoptosis potentially outweighs proliferation by a factor of 2 8-fold, when examined over the same time period. Consequently, even small changes in the finite numbers of apoptotic cells become highly significant. Our results have shown the definite role of apoptosis within progression of renal damage and highlighted how it may contribute to the progression of tubular atrophy and play a role in the pathogenesis of tubulo-interstitial scarring.     

Identification and characterization of nuclear pore subcomplexes in mitotic extract of human somatic cells

BACKGROUND: Flaxseed has demonstrated useful antiinflammatory properties in a number of animal models and human diseases. We undertook a study to determine if flaxseed would also modify clinical course and renal pathology in the Han:SPRD-cy rat. METHODS: Male Han:SPRD-cy rats were pair fed a 10% flaxseed of control rat chow diet for eight weeks from weaning. Tissue was harvested for analysis of cystic change, apoptosis, cell proliferation, and fibrosis. Tissue was also harvested for lipid analysis using gas chromatography. RESULTS: Animals thrived on both diets. Flaxseed-fed animals had lower serum creatinine (69 vs. 81 mumol/liter, P = 0.02), less cystic change (1.78 vs. 2.03 ml/kg, P = 0.02), less renal fibrosis (0.60 vs. 0.93 ml/kg, P = 0.0009), and less macrophage infiltration (13.8 vs. 16.7 cells/high-power video field) of the renal interstitium than controls. The groups did not differ in renal tubular epithelial cell apoptosis and proliferation. Lipid analysis revealed significant renal enrichment of 18 and 20 carbon omega 3 polyunsaturated fatty acids (total omega 6:omega 3 ratio 3.6 vs. 9.1, P < 0.0001). CONCLUSIONS: Flaxseed ameliorates Han:SPRD-cy rat polycystic kidney disease through moderation of the associated chronic interstitial nephritis. The diet alters renal content of polyunsaturated fatty acids in a manner that may promote the formation of less inflammatory classes of renal prostanoids.     

A case report of glomerulocystic kidney disease with hypothyroidism in a new born infant

We report a rare case of glomerulocystic kidney disease (GCKD) with congenital hypothyroidism. A gigantic abdominal mass was noted at birth. There was no family history of renal cystic disease. Ultrasonography revealed diffuse granular cysts in the markedly enlarged kidneys. Blood examination showed moderate renal failure and hypothyroidism. Bilateral nephrectomy was conducted at 47 days of age to relieve respiratory failure and severe abdominal distention caused by the growing cystic kidneys. Histological findings of the kidney showed numerous glomerular cysts without renal dysplasia. There were no other malformations. These findings were compatible with GCKD.     

Current concepts and controversies in imaging of renal cystic diseases

Renal cystic disease compromises a diverse group of inherited and acquired entities. This article reviews the clinical, pathologic, and radiologic findings of eight renal cystic diseases. For each entity, the current concepts of pathogenesis and pathophysiology are discussed. When appropriate, controversies concerning terminology, management, and malignant potentials are addressed. Renal cystic diseases that are discussed include autosomal dominant and autosomal recessive polycystic kidney disease, medullary sponge kidney, medullary cystic disease, multicystic, dysplastic kidney, von Hippel-Lindau disease, acquired cystic kidney disease, and tuberous sclerosis.     

Sodium pump distribution is not reversed in the DBA/2FG-pcy, polycystic kidney disease model mouse

Recently, it has been reported that Na,K-ATPase in the renal epithelia of human autosomal dominant polycystic kidney disease and cpk mouse, a murine model of autosomal recessive polycystic kidney disease, mislocates to apical plasma membrane and that mislocated Na,K-ATPase causes the cyst formation. Whether the DBA/2FG-pcy mice, which are presumably a suitable model for autosomal dominant polycystic kidney disease, also exhibit the reversal polarity of Na,K-ATPase localization was examined. Kidneys of newborn DBA/2FG-pcy mice, and those at early and late stages of cyst development were examined by immunohistochemical techniques. At any stage, abnormal distribution of Na,K-ATPase on the apical membranes of tubular epithelial cells could not be detected. It is suggested that cysts can be formed without reversed polarity of Na,K-ATPase distribution in pcy mice.     

A constitutive law for mitral valve tissue

BACKGROUND: Obstructive nephropathy is a primary cause of renal failure in infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal rat results in reduced renal expression of epidermal growth factor (EGF), renal tubular epithelial (RTE) cell apoptosis and interstitial fibrosis. We wished to determine whether these changes could be prevented by exogenous administration of EGF. METHODS: Thirty-three Sprague-Dawley rats underwent UUO within the first 48 hours of life, and received daily injections of either EGF (0.1 mg/kg/day) or saline (control) for the following seven days, after which obstructed and intact opposite kidneys were removed for study. These were compared to 11 sham-operated rats that received either no injections, EGF injections, or saline injections. Renal cell proliferation was determined by proliferating cell nuclear antigen, apoptosis was measured by the TUNEL technique, and the distribution of vimentin, clusterin, transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth muscle actin were determined by immunohistochemistry. Tubular dilation, tubular atrophy, and interstitial collagen deposition were quantitated by histomorphometry. RESULTS: Compared to controls, EGF treatment increased RTE cell proliferation in the obstructed kidney by 76%, decreased apoptosis by 80%, and reduced vimentin, clusterin and TGF-beta 1 immunostaining (all P < 0.05). EGF treatment reduced tubular dilation by 50%, atrophic tubules by 30%, and interstitial fibrosis by 50% (all P < 0.05). There was no significant effect of EGF on renal alpha smooth muscle actin distribution. There was no effect of saline or EGF injections on kidneys from sham-operated rats for any of the parameters studied. CONCLUSIONS: We conclude that EGF stimulates RTE cell proliferation and maturation and reduces apoptosis in the neonatal rat kidney subjected to chronic UUO. These effects may contribute to the reduction in tubular dilation, tubular atrophy, and interstitial fibrosis. By preserving renal development, administration of EGF attenuates the renal injury resulting from chronic UUO.     

High prevalence of rheumatoid factor in community-based series of patients with rheumatoid arthritis meeting the new (1987) ARA criteria: RF-negative non-erosive rheumatoid arthritis is very rare

The possible relation of acquired cystic kidney disease to renal cell carcinoma resulted in an interdisciplinary concern about this disease. Kidneys from 125 autopsies of dialysis patients were studied. Twenty-four of the patients had tumors. Beside four renal adenocarcinomas and two urothelial carcinomas, incidental small tumor nodules were described in 15.1%. Men had more nodules than women. Patients with nodules had a higher average cyst count, often with multi-layered epithelium. There was no difference in age or time of dialysis. This suggests a factor which mediates cyst and tumor proliferation, independent from the time of dialysis. With the improvement in imaging techniques, an increasing number of small renal tumors will be found. Further studies are necessary to evaluate the risk of small kidney cell tumors and their association with acquired cystic kidney disease.     

Late occurrence of cysts in autosomal dominant medullary cystic kidney disease

Medullary cystic kidney disease (MCD) is characterized by multiple renal cysts at the corticomedullary boundary area, by autosomal dominant inheritance, and by onset of chronic renal failure in the third decade of life. We report on a family with three affected individuals of both sexes in two generations presenting with end-stage renal failure at age 22-31 years. Primarily diagnoses considered included unclassified hereditary nephropathy and autosomal dominant polycystic kidney disease. Careful evaluation of all findings, initiated after investigation of renal morphology with CT, revealed features characteristic for MCD and led to the final diagnosis of MCD. We conclude that MCD is an important differential diagnosis for polycystic kidney disease in young adults with end-stage renal failure. Establishing the correct diagnosis has considerable impact for genetic counselling.