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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Once viewed as hopelessly incurable disorders and the dustbin for careers in academic medicine, the polycystic kidney diseases have emerged as prime targets of pathophysiologic study and palliative and definitive treatment in the era of molecular medicine. Polycystic kidney disease (PKD) may be hereditary or acquired. The major inherited types are autosomal dominant (AD) and autosomal recessive (AR). ADPKD is caused by at least two (and possibly three) genes located on separate chromosomes, while ADPKD-1 is due to a 14 kb transcript in a duplicated region on the short arm of chromosome 16 very near the alpha-globin gene cluster and the gene for one form of tuberous sclerosis. ADPKD-2 has been assigned to the long arm of chromosome 4. ARPKD is due to a mutated gene on both copies of the long arm of chromosome 6. Cysts originate in renal tubules. Proliferation of tubule epithelial cells modulated by endocrine, paracrine, and autocrine factors is a major element in the pathogenesis of renal cystic diseases. In addition, fluid that is abnormally accumulated within the cysts is derived from glomerular filtrate and, to a greater extent, by transepithelial fluid secretion. Abnormal synthesis and degradation of matrix components associated with interstitial inflammation are additional features in the pathogenesis of renal cystic diseases. The ADPKD genotypes are characterized by bilateral kidney cysts, hypertension, hematuria, renal infection, stones, and renal insufficiency. ADPKD is a systemic disorder; cysts appear with decreasing frequency in the kidneys, liver, pancreas, brain, spleen, ovaries, and testis. Cardiac valvular disorders, abdominal and inguinal hernias, and aneurysms of cerebral and coronary arteries and aorta are also associated with ADPKD. Treatment is supportive: dietary regulation of salt and protein intake, control of hypertension and renal stones, and dialysis and transplantation at the end stage. ARPKD is a relatively rare disease that causes clinical symptoms at birth, with significant mortality in the first month of life. The cysts develop primarily in the collecting ducts because of a failure in the maturation process. Early complications include Potter's syndrome; excessive size of the kidneys, causing respiratory dysfunction; hypertension; and renal insufficiency. Hepatic fibrosis is an associated extrarenal problem that results in significant morbidity in young children and adolescents. Treatment includes supportive care, dialysis, and renal transplantation. Acquired cysts (solitary/simple) are commonplace in older persons. Multiple cysts may be seen in association with potassium deficiency, congenital disorders, metabolic diseases, and toxic renal injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Polycystic kidney disease: etiology, pathogenesis, and treatment. 758 86

Congenital hepatic fibrosis (CHF) is an uncommon autosomal recessive malformation. It may be associated with extrahepatic manifestations such as polycystic kidney disease. The main consequence is portal hypertension and bleeding from varices. Despite liver transplantation as a therapeutic option for this patient, long-term impact of liver transplantation on renal functions of patients with autosomal recessive polycystic kidney disease with associated liver disease is not well known. In this study, we aimed to analyze the patient's renal function after liver transplantation by creatinine clearance, glomerular filtration rate, and renal resistive indexes. Between March 1997 and September 2002, three of 50 orthotopic liver transplantation (OLT) were performed because of CHF associated with ARPKD at Ege University Organ Transplantation and Research Center. Baseline immunosuppression consisted of prednisone and cyclosporine A (CSA). The mean follow-up of the patients was 2.1 yr. Blood urea and creatinine levels were decreased after operation in all patients and remained within the normal range at the sixth and 12th month, whereas the level of the third patient were increased at the 18th month. RRI values of patients were not found different at the sixth month whereas, RRI values of patients were decreased at the 12th month and remained unchanged at the 18th month of follow-up. During the study period hypertension developed in one patient at the 16th month and resolved with antihypertensive treatment and decreasing dosage of CSA. Kidney function has remained satisfactory in all of the patients despite the use of cyclosporine. OLT can provide good survival in patients with CHF associated with ARPKD.
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PMID:Impact of liver transplantation on renal function of patients with congenital hepatic fibrosis associated with autosomal recessive polycystic kidney disease. 1559 23

Improved neonatal medical care and renal replacement technology have improved the long-term survival of patients with ARPKD. Ten-yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life. In addition to renal pathology, patients with ARPKD develop ductal plate malformations with cystic dilation of intra- and extrahepatic bile ducts resulting in CHF and Caroli syndrome. Many patients with CHF will develop portal hypertension with resulting esophageal varices, splenomegaly, hypersplenism, protein losing enteropathy, and gastrointestinal bleeding. Management of portal hypertension may require EBL of esophageal varices or porto-systemic shunting. Complications of hepatic involvement can include ascending cholangitis, cholestasis with malabsorption of fat-soluble vitamins, and rarely benign or malignant liver tumors. Patients with ARPKD who eventually reach ESRD, and ultimately require kidney transplantation, present a unique set of complications related to their underlying hepato-biliary disease. In this review, we focus on new approaches to these challenging patients, including the indications for liver transplantation in ARPKD patients with severe chronic kidney disease awaiting kidney transplant. While survival in patients with ARPKD and isolated kidney transplant is comparable to that of age-matched pediatric patients who have received kidney transplants due to other primary renal diseases, 64-80% of the mortality occurring in ARPKD kidney transplant patients is attributed to cholangitis/sepsis, which is related to their hepato-biliary disease. Recent data demonstrate that surgical mortality among pediatric liver transplant recipients is decreased to <10% at one yr. The immunosuppressive regimen used for kidney transplant recipients is adequate for most liver transplant recipients. We therefore suggest that in a select group of ARPKD patients with recurrent cholangitis or complications of portal hypertension, combined liver-kidney transplant is a viable option. Although further study is necessary to confirm our approach, we believe that combined liver-kidney transplantation can potentially decrease overall mortality and morbidity in carefully selected ARPKD patients with ESRD and clinically significant CHF.
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PMID:New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications. 2359 29

Genetic disorders of the kidney include cystic diseases, metabolic diseases and immune glomerulonephritis. Cystic diseases include autosomal dominant and recessive polycystic kidney disease (ADPKD, ARPKD, respectively). Neonates with enlarged, cystic kidneys should be evaluated for PKD. Patients with ADPKD have cysts and renal enlargement. Most patients present with hypertension, hematuria or flank pain; the most common extrarenal manifestation is polycystic liver disease. Oligohydramnios, bilaterally enlarged kidneys and decreased urine are featured in utero in ARPKD. Medullary sponge kidney is uncommon and features nephrocalcinosis, recurrent calcium stones and a history of polyuria/nocturia and/or urinary tract infections. Alport syndrome (AS) is an inherited disease of the glomerular basement membrane that is usually inherited as an X-linked dominant trait. Most patients with AS present in the first two decades of life with persistent microscopic or gross hematuria. Later, proteinuria is seen and its presence portends disease progression. Other findings may include sensorineural hearing loss and ocular abnormalities. There are various inherited tubulopathies, including Bartter syndrome, a group of renal tubular disorders that consist of two phenotypes with four genotypes. Patients usually present early in life with salt wasting, hypokalemia and metabolic alkalosis. Other features, depending on genotype, may include polyhydramnios and premature birth. Gitelman syndrome is also a salt-losing tubulopathy characterized by hypokalemic alkalosis. The majority of patients with Gitelman syndrome present during adolescence or early adulthood.
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PMID:Inherited renal diseases. 2508 62