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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal dominant polycystic kidney disease (ADPKD) is a common systemic genetic disease which comprises 8 to 10% of patients treated by dialysis and transplantation. Breakthroughs in molecular genetics and cell biology have led to new insights into cyst formation and growth. Until the specific genetic defects are identified, the management of this disorder will necessarily be empiric. This paper discusses current management strategies in ADPKD focusing on hypertension, hematuria, pain and infection. Special considerations for management of end-stage renal failure in patients with ADPKD are also reviewed.
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PMID:Clinical management of autosomal dominant polycystic kidney disease. 836 Nov 35

Kaspareit-Rittinghausen described a rodent model of inherited polycystic kidney disease (PKD), the Han:SPRD rat [1, 2], in which heterozygotes develop renal cysts and renal failure (in males) over several months, whereas homozygous animals develop rapidly progressive renal enlargement that leads to death in a few weeks. In this study, we examined selected elements of the pathogenesis of this disease in heterozygotes and homozygotes from birth to advanced disease. Heterozygous male rats developed slowly progressive renal cystic disease with interstitial fibrosis and azotemia seen by six months of age. Female heterozygotes developed slowly progressive renal cystic disease, but did not develop interstitial fibrosis or azotemia. Epithelial cells lining cyst cavities showed various degrees of morphologic immaturity. Cyst walls also developed basement membrane thickening, especially in areas of cellular immaturity, suggesting an interrelationship between this basement membrane thickening and cellular dedifferentiation. Thickened basement membranes were associated with increased immunoreactivity for type IV collagen, laminin, and fibronectin. Homozygous rats developed massive renal enlargement, marked azotemia, and died near three weeks of age. Renal c-myc proto-oncogene expression was elevated in homozygous cystic infants and in adult heterozygotes. In situ hybridization showed high levels of c-myc mRNA in cyst epithelia, suggesting abnormal regulation of cellular proliferation in the cells lining cysts, as seen in other models of PKD. The Han:SPRD rat is the only well-documented animal model of inherited PKD with an autosomal-dominant inheritance pattern and appears to have several features which resemble human ADPKD.
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PMID:Autosomal-dominant polycystic kidney disease in the rat. 845 52

It has been claimed that anticipation occurs in ADPKD, i.e. endstage renal failure at progressively earlier age in successive generations. This observation might possibly point to unstable DNA as the molecular basis of ADPKD. We analysed 74 parent-offspring pairs of 148 families in Germany and Austria in whom (i) ADPKD was verified by appropriate imaging procedures and (ii) age at renal death was accurately known. The median difference for age at renal death between parent and offspring was 0 years, range -26.3 to +27.2 years. There was no deviation from normal (Gaussian) distribution according to the Shapiro-Wilk test (P = 0.75). We conclude that systematic anticipation cannot be demonstrated with this sample which had sufficient size for meaningful biostatistical analysis.
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PMID:Anticipation of age at renal death in autosomal dominant polycystic kidney disease (ADPKD)? 855 77

Autosomal dominant polycystic kidney disease is one of the most commonly inherited diseases in the United States. It affects nearly 500,000 Americans and accounts for 5 to 10 percent of patients with end-stage renal disease. Diagnosis is usually made in middle age, when complications such as hypertension, pain and hematuria develop. Renal complications include hypertension, cyst infection and hemorrhage, hematuria and flank pain. Other manifestations and related conditions include polycystic liver disease, cerebral aneurysm, cardiac valve abnormalities and diverticulosis. The severity and course of the disease vary in individual patients. Management involves the control of hypertension and treatment of complications. Genetic counseling is important. Dialysis and renal transplantation often are successful treatments in patients who develop renal failure.
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PMID:Autosomal dominant polycystic kidney disease. 859 59

Autosomal dominant polycystic kidney disease (ADPKD) is caused by at least two different genes. The ADPKD1 gene is located on chromosome 16p and a second locus is at 4q. Although the ADPKD1 gene is responsible for the majority of the disease in whites, there was no information regarding the gene type in blacks. We studied a black family which presented with both ADPKD and sickle-cell trait (SA) to determine which ADPKD gene was present in this family, and to examine linkage between the ADPKD in this family and markers for the beta-hemoglobin gene on chromosome 11. The ADPKD in this family was linked to markers on chromosome 16, and no linkage was found with the beta-hemoglobin gene. Family members with SA and ADPKD had an early onset of end-stage renal disease. The hemoglobin haplotype was identified as the Central African Republic-type, which has been reported to be associated with a higher incidence of renal failure in sickle-cell anemia.
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PMID:Genetic studies in a black family with autosomal dominant polycystic kidney disease and sickle-cell trait. 873 Apr 27

Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.
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PMID:Factors influencing progression of renal failure in autosomal dominant polycystic kidney disease. 874 91

Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene disorder resulting in renal failure. It is generally an adult onset disease, but rarely, cases of severe childhood polycystic disease arise in ADPKD families. The clear clinical anticipation in these pedigrees has led to the suggestion that the mutation may be an unstable trinucleotide repeat. We have now identified a nonsense mutation, Tyr3818Stop, in one such family (P117) within the major ADPKD gene, polycystic kidney disease 1 (PKD1). The mutation is shown to be a de novo change in the father, and of grandpaternal origin. PKD1 manifests as typical adult onset disease in the father, but is seen as severe disease, detected as enlarged polycystic kidneys in utero, in one of a pair of dizygotic twins; the other twin has the mutation but no evidence of cysts, consistent with an adult onset disease course. The finding of the same stable mutation associated with very different disease severity in this family indicates that phenotypic variation in PKD1 is not due to a dynamic mutation. It seems most likely that a small number of modifying factors may radically affect the course of disease in PKD1; identification of such factors will have important prognostic implications in this disorder.
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PMID:A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1). 884 49

Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneous disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidney failure. Three genes are implicated in causing ADPKD. One on chromosome 16, PKD1, accounts for 85-90% of all cases, and the PKD2 gene on chromosome 4 accounts for the remainder. A very rare third locus is still of unknown location. We used PKD1- and PKD2-linked polymorphic markers to make the diagnosis of ADPKD in young presymptomatic members in affected families. We showed that in young members of families where clinical diagnosis cannot be definitively established, molecular linkage analysis can assist clinicians in the diagnosis. In one family a 24-year old had one cyst on the right kidney; however, molecular analysis showed clearly that he had inherited the normal haplotype. In another family, in one part of the pedigree there was co-inheritance of the disease with a PKD1-linked haplotype which originated in a non-affected 78-year-old father. Analysis with PKD2-linked markers excluded this locus. The data can be explained in one of two ways. Either this family phenotype is linked to a third locus, or the proband was the first affected person, most probably because of a novel mutation in one of her father's chromosomes. In conclusion, the combined use of markers around the PKD1 and the PKD2 locus provides more definitive answers in cases where presymptomatic diagnosis is requested by concerned families.
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PMID:Presymptomatic molecular diagnosis of autosomal dominant polycystic kidney disease using PKD1- and PKD2-linked markers in Cypriot families. 889 80

Autosomal dominant polycystic kidney disease (ADPKD) is a common disease and an important cause of renal failure. It is characterized by considerable intrafamilial phenotypic variation and focal cyst formation. To elucidate the molecular basis for these observations, we have developed a novel method for isolating renal cystic epithelia from single cysts and have used it to show that individual renal cysts in ADPKD are monoclonal. Loss of heterozygosity was discovered within a subset of cysts for two closely linked polymorphic markers located within the PKD1 gene. Genetic analysis revealed that it was the normal haplotype that was lost. This study provides a molecular explanation for the focal nature of cyst formation and a probable mechanism whereby mutations cause disease. The high rate at which "second hits" must occur to account for the large number of cysts observed suggests that unique structural features of the PKD1 gene may be responsible for its mutability.
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PMID:The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. 897 3

Polycystic kidney disorders are more common than once appreciated, are contributors to significant morbidity, are potentially fatal and are costly to treat. In the past few years much progress has been made toward understanding the pathogenesis of renal cystic disorders. The dominantly inherited disorders are initiated by mutations within genes located in chromosomes 16 and 4 (ADPKD) that cause the kidneys to enlarge several-fold greater than normal. This enlargement is owing to the proliferation of epithelial cells in tubule segments, to the accumulation of fluid within the dilated tubule segment created by the proliferating cells, and to remodelling of the extracellular matrix. The focal beginning of ADPKD in a relatively few renal tubules suggests that the cells in the walls of cysts may reflect clonal growth and that this aberrant proliferation may be secondary to a somatic "second hit" process. The rate at which the cysts enlarge appears to depend on endocrine, paracrine and autocrine factors that drive cellular proliferation and transepithelial fluid secretion within the cysts. The presence of the renal cysts within certain kidneys appears to provoke interstitial inflammation and apoptosis that contribute to fibrosis and renal insufficiency in approximately one-half of persons with ADPKD. Why renal cysts do not cause renal failure in the other one-half of patients with polycystic kidneys is a provocative question that awaits further study.
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PMID:Polycystic kidney disease: huge kidneys, huge problems, huge progress. 910 75


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