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At least 19 recordsLinked to original sources
PubMed2006

Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion cast study.

Autosomal-dominant polycystic kidney disease (ADPKD) accounts for about 10% of all cases of chronic renal failure requiring dialysis. The disease is characterized by proliferation of renal epithelial cells and formation of cysts that expand over years and replace the normal parenchyma of the kidney. As the cysts grow, the volume of the kidney can increase by more than 10-fold, implying that remodeling and expansion of the vasculature must occur to provide oxygenation and nutrition to the cyst cells. Our previous studies support the notion that there is angiogenesis in ADPKD. We report here results from resin casting of ADPKD kidneys vasculature. In this study, the corrosion-casting method was used in conjunction with scanning electron microscopy to study the vascular architecture and the evidence for angiogenesis in ADPKD kidneys. We found a well-defined vascular network around the cysts forming a 'vascular capsule' somewhat similar to that described in avascular leiomyomata. We also found that the normal vascular architecture is lost and replaced by an assortment of capillaries of larger size than those in the normal kidney, mixed with flattened and spiral arterioles, damaged glomeruli, and atresic venules, indicative of regression of the microvasculature. In the same areas, there was capillary sprouting, considered the hallmark of angiogenesis. The present study documents regression changes of the vasculature and confirms the existence of angiogenesis in ADPKD kidneys, and suggests the use of inhibitors of angiogenesis as a possible avenue for the treatment of the disease.

Adult↗
PubMed2006

Early embryonic renal tubules of wild-type and polycystic kidney disease kidneys respond to cAMP stimulation with cystic fibrosis transmembrane conductance regulator/Na(+),K(+),2Cl(-) Co-transporter-dependent cystic dilation.

Metanephric organ culture has been used to determine whether embryonic kidney tubules can be stimulated by cAMP to form cysts. Under basal culture conditions, wild-type kidneys from embryonic day 13.5 to 15.5 mice grow in size and continue ureteric bud branching and tubule formation over a 4- to 5-d period. Treatment of these kidneys with 8-Br-cAMP or the cAMP agonist forskolin induced the formation of dilated tubules within 1 h, which enlarged over several days and resulted in dramatically expanded cyst-like structures of proximal tubule and collecting duct origin. Tubule dilation was reversible upon withdrawal of 8-Br-cAMP and was inhibited by the cAMP-dependent protein kinase inhibitor H89 and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR(inh)172. For further testing of the role of CFTR, metanephric cultures were prepared from mice with a targeted mutation of the Cftr gene. In contrast to kidneys from wild-type mice, those from Cftr -/- mice showed no evidence of tubular dilation in response to 8-Br-cAMP, indicating that CFTR Cl(-) channels are functional in embryonic kidneys and are required for cAMP-driven tubule expansion. A requirement for transepithelial Cl(-) transport was demonstrated by inhibiting the basolateral Na(+),K(+),2Cl(-) co-transporter with bumetanide, which effectively blocked all cAMP-stimulated tubular dilation. For determination of whether cystic dilation occurs to a greater extent in PKD kidneys in response to cAMP, Pkd1(m1Bei) -/- embryonic kidneys were treated with 8-Br-cAMP and were found to form rapidly CFTR- and Na(+),K(+),2Cl(-) co-transporter-dependent cysts that were three- to six-fold larger than those of wild-type kidneys. These results suggest that cAMP can stimulate fluid secretion early in renal tubule development during the time when renal cysts first appear in PKD kidneys and that PKD-deficient renal tubules are predisposed to abnormally increased cyst expansion in response to elevated levels of cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

[Endothelins: possibly a new pharmacological approach in cardiovascular diseases, kidney diseases and oncological disorders].

Only 10 years ago, the vasoconstricting peptide endothelin was discovered; it is produced by endothelial cells. Different isoforms and receptors of endothelin have been identified. The effects of endothelin-I, the most important isoform, are mainly vasoconstriction and proliferation of cells. In the last few years endothelin receptor antagonists have become available, which can delineate the clinical importance of the endothelin system. Possible indications for endothelin receptor blockers are renal disease (acute and chronic renal failure) and cardiovascular disease (heart failure; restenosis after percutaneous transluminal coronary angioplasty (PTCA); pulmonary hypertension; systemic hypertension). There is also a possible role for endothelin receptor blockers in oncology (prostatic carcinoma). Currently clinical trials are being carried out to determine the efficacy of these compounds for the above-mentioned indications.

Cardiovascular Diseases↗
PubMed2002

Kidney injury molecule-1 expression in murine polycystic kidney disease.

Kidney injury molecule-1 (Kim-1) is a type 1 membrane protein maximally upregulated in proliferating and dedifferentiated tubular cells after renal ischemia. Because epithelial dedifferentiation, proliferation, and local ischemia may play a role in the pathophysiology of autosomal dominant polycystic kidney disease, we investigated Kim-1 expression in a mouse model of this disease. In the Pkd2(WS25/-) mouse model for autosomal dominant polycystic kidney disease, cystic kidneys show markedly upregulated Kim-1 levels compared with noncystic control kidneys. Kim-1 is present in a subset of cysts of different sizes and segmental origins and in clusters of proximal tubules near cysts. Kim-1-expressing tubular cells show decreased complexity and quantity of basolateral staining for Na-K-ATPase. Other changes in polarity characteristic of ischemic injury are not present in Kim-1-expressing pericystic tubules. Polycystin-2 expression is preserved in Kim-1-expressing tubules. The interstitium surrounding Kim-1-expressing tubules shows high proliferative activity and staining for smooth muscle alpha-actin, characteristic of myofibroblasts. Although the functional role of the protein in cysts remains unknown, Kim-1 expression in tubules is strongly associated with partial dedifferentiation of epithelial cells and may play a role in the development of interstitial fibrosis.

Amino Acid Sequence↗
PubMed2005

Epidemiology and risk factors for chronic kidney disease.

Kidney disease is highly prevalent in the United States population and groups at high risk for increased prevalence of CKD include individuals with a family history of ESRD, diabetes, hypertension, and cardiovascular disease. Despite the increased risk of ESRD observed for blacks compared with whites, racial disparities in the prevalence of kidney disease have not been consistently demonstrated in the United States population. Although the reasons for discrepancy in risk of ESRD and CKD have not been established, clinicians should be aware that more rapid progression of CKD among blacks is a possible explanation for this observation and that closer monitoring and intensive care of risk factors associated with progressive renal injury is warranted for blacks with CKD and in other high-risk groups. Therapeutic interventions that delay or prevent progressive kidney disease are well established and incorporated into widely disseminated clinical practice guidelines. These interventions include aggressive blood pressure control with agents that block the renin-angiotensin system, reduction of dietary protein to recommended levels for the American diet, weight loss, smoking cessation, and control of hyperlipidemia. These interventions also reduce the risk of cardiovascular disease and should be regarded as essential components of care of CKD. Achieving high levels of medically appropriate care of CKD patients and reduction in risk of progression to ESRD may be delayed by barriers created by individual and regional poverty.

Humans↗
PubMed1990

Animal models of spontaneous diabetic kidney disease.

Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel-Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease.

Animals↗
PubMed2005

Novel non-rodent models of kidney disease.

Kidney disease in the 21(st) century affects increasing numbers of individuals. We continue to be challenged by our lack of understanding of the pathophysiology of acute and chronic renal disease including genetic diseases involving the kidney. Rodent knockout animals or inbred strains have greatly contributed to our understanding of many monogenetic and complex diseases. Non-rodent animal models of disease have become more attractive since genomic data has become available for a variety of organisms that offer distinct advantages over mice and rats for ease in conducting high-throughput chemical or mutagenesis screens. It is thus timely to examine the physiology and pathophysiology of the kidney or kidney equivalents in these organisms to evaluate their relevance as models for human disease. In addition to organisms whose small size and accessibility facilitate large scale screening approaches, larger animals at the other end of the spectrum offer unique physiological advantages in both size equivalency to humans as well as, in some cases, physiological and pathophysiological responses that closely mimic those of humans. Here we review a selected number of non-rodent experimental models of kidney diseases, focusing on recent advances in the use of the worm Caenorhabditis elegans, the fruitfly Drosophila melanogaster, the zebrafish Danio rerio, the little skate Leucoraja erinacea, the MGH miniature swine, merino cross sheep, and the cow Bos taurus to study kidney disease.

Acute Kidney Injury↗
PubMed1978

Hereditary polycystic kidney disease (adult form): a microdissection study of two cases at an early stage of the disease.

Kidney fragments from two cases of hereditary polycystic kidney disease (adult form) at an early stage were examined by microdissection. Localized cystic cystic dilatations were found in proximal and distal tubules, loops of Henle, and collecting tubules. Entirely normal nephrons and collecting tubules were also observed. Abnormal branching of collecting tubules or the abnormal attachment of nephrons, as described in other microdissection studies, were not found. Our observations do not confirm the hypothesis that the adult form of hereditary polycystic kidney disease is the consequence of ampullary dysfunction during early development.

Adult↗
PubMed2005

Clinical evidence for the influence of uric acid on hypertension, cardiovascular disease, and kidney disease: a statistical modeling perspective.

This article critically evaluates the clinical evidence regarding the influence of uric acid on hypertension, cardiovascular disease, and kidney disease. Data on these relationships are largely observational and exceedingly complex. The complexity is owing to indirect and direct relations, and bidirectional influences, simultaneously operating on multiple outcomes. Limitations of previous analyses include inadequate statistical methods using only bivariate correlations or poorly specified multiple regression models. As a result, great controversy developed as to whether uric acid is an independent predictor of important outcomes. An example of such analytic limitations is including hypertension as an independent variable, together with uric acid, in a multivariate model for predicting cardiovascular disease. Hypertension may predict significant variance in cardiovascular disease, but the contribution of uric acid may not be recognized if uric acid exerts its influence indirectly through hypertension. Path analysis, which can model direct and indirect influences on outcomes simultaneously, would address this substantive question. Studies of uric acid in relation to hypertension, cardiovascular disease, and kidney disease using a path-analytic approach would help specify such conditions as well as optimize design of clinical trials to determine if decreasing uric acid levels improves outcomes.

Cardiovascular Diseases↗
PubMed2006

Analysis of cardiovascular disease and kidney outcomes in multidisciplinary chronic kidney disease clinics: complex disease requires complex care models.

PURPOSE OF REVIEW: Chronic kidney disease is recognized as being highly prevalent in the population, and associated with morbidity and mortality relative to the general population. The complexity of patients and the multiplicity of interventions required to maintain health has forced clinicians to develop different models of healthcare delivery. This publication reviews the current literature on specific interventions to reduce progression of chronic kidney disease and cardiovascular disease, and studies the examination of outcomes of patients exposed to different healthcare delivery models. Specifically we examine the rationale and outcomes of those seen in multidisciplinary clinics. RECENT FINDINGS: Current evidence supports the use of rennin-angiotensin system blockers, reduction of blood pressure and proteinuria and phosphate control. Additional less robust studies support the need for attention to anemia, hyperparathryoidism, and other more "kidney specific" risk factors. The attendance of identified chronic kidney disease patients at multidisciplinary clinics appears to improve survival once dialysis is started. Despite aggressive management, not all patients are able to meet clinical targets associated with improved outcomes. SUMMARY: The recognition of the complexity of chronic kidney disease care and the need to develop and test models of care in addition to the single interventions is a challenge for both researchers and clinicians. Current data support the use of multidisciplinary clinics in improving outcomes of referred patients. Future research will help to refine and define appropriate care models for this growing chronic kidney disease population.

Calcium↗