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PubMed2005

Kidney disease among the Zuni Indians: the Zuni Kidney Project.

BACKGROUND: There is an epidemic of kidney disease among the Zuni Indians. In collaboration with health care providers and research institutions, the Zuni Pueblo established the Zuni Kidney Project to reduce the burden of kidney disease. METHODS: The Zuni Kidney Project conducted a population-based, cross-sectional survey to estimate the prevalence of albuminuria, hematuria, and related risk factors. Neighborhood household clusters served as the sampling frame. Participants completed a questionnaire, donated blood and urine samples, and had blood pressure, height, and weight measured. This survey provided the foundation for ongoing studies to identify genetic and environmental risk factors for disease susceptibility and progression. RESULTS: Age and gender distributions among survey participants were similar to those in the eligible Zuni population. Prevalence of incipient albuminuria (IA) (0.03< or = urine albumin:creatinine ratio, UACR <0.3) and overt albuminuria (OA) (UACR < 0.3) were higher among diabetics [IA 34.3% (28.3, 40.4%); OA 18.6% (13.7, 23.6%)] than nondiabetics [IA 11.1% (9.3, 12.8%); OA 1.7% (1.0, 2.5%)]. Nondiabetics comprised 58.6% (52.2, 65.0%) and 30.9% (19.9, 41.9%) of participants with IA and OA, respectively. The prevalence of hematuria was higher among diabetics [> or = trace 47.0% (40.7, 53.4); > or =50 red blood cell/microL 25.8% (20.3, 31.4%)] than nondiabetics [> or = trace 31.1% (28.5, 33.7%); > or =50 red blood cell/microL 16.6% (14.5, 18.7%)]. Hypertension was associated with albuminuria among diabetic and nondiabetic participants. Hypercholesterolemia was associated with albuminuria among nondiabetic participants. Diabetes and alcohol use were associated with hematuria. CONCLUSION: The high prevalences of albuminuria among nondiabetics and of hematuria among diabetics and nondiabetics are consistent with high rates of nondiabetic kidney disease among Zuni Indians with and without diabetes.

Adult↗
PubMed2004

The spectrum of cardiovascular disease in children with predialysis chronic kidney disease.

Cardiovascular disease is the major cause of mortality in adults and children on chronic dialysis and in adults after kidney transplantation. Cardiovascular disease burden and cardiovascular mortality are high in adults with chronic kidney disease. The early development of cardiovascular disease risk factors, some of which are modifiable, largely explain this phenomenon. Limited data are available on the prevalence of chronic kidney disease in children, the prevalence of cardiovascular disease in children with chronic kidney disease, and the prevalence of cardiovascular disease risk factors in these patients. This article summarizes the current knowledge of the prevalence of cardiovascular disease and of cardiovascular disease risk factors in pediatric patients with predialysis chronic kidney disease. Long-term prospective studies are needed to determine the impact of early identification and treatment of cardiovascular disease and its risk factors on the natural history of cardiovascular disease in children with chronic kidney disease.

Anemia↗
PubMed1977

Renin-dependent hypertension in patients with unilateral kidney disease not caused by renal artery stenosis.

The practical value of renin secretion studies in hypertension associated with unilateral kidney disease, other than renal artery stenosis, has not been documented. This study, comprising 19 patients of this kind, disclosed three who had an abnormal renin secretion from the diseased kidney. The level of peripheral renin under basal conditions, and the change from this level as a result of provocation of renin secretion, were used to evaluate the importance of an arteriovenous renin gradient in the diseased kidney. The three patients were the only ones to become normotensive when the diseased kidney was removed in seven of the cases studied. When nephrectomy is considered in severe hypertension with unilateral kidney disease, there is a place for renin secretion studies, but a screening procedure is advisable. Measuring peripheral renin under basal conditions and after provocation of renin secretion, should reveal whether the renin-angiotensin system might be playing a part in maintaining the high BP. The finding of diminishing kidney function in many of the patients, despite good BP control, emphasizes the importance of sparing kidney function whenever possible.

Adolescent↗
PubMed2000

Acquired cystic kidney disease.

Acquired cystic kidney disease (ACKD), also known as acquired renal cystic disease (ARCD,) occurs in patients who are on dialysis for end-stage renal disease. It is generally accepted that ACKD develops as a consequence of sustained uremia and can first manifest even before dialysis is initiated while the patient is still in chronic renal failure. The role of immune suppression, particularly in transplant recipients, in the development of ACKD, is still under investigation. The prevalence of ACKD is directly related to the duration of dialysis and the risk of cancer is directly related to the presence of cysts. Herein we review the current understanding of the pathophysiology and imaging implications of ACKD.

Diagnostic Imaging↗
PubMed2004

The chronic kidney disease initiative.

The Chronic Kidney Disease Initiative was implemented at the request of the Council of American Kidney Societies to formulate a plan of action to solve many of the perceived problems associated with identifying, caring for, and attaining the best outcomes for patients with chronic kidney disease. With the assistance of a community of stakeholders and a formalized workshop and process, the Chronic Kidney Disease Initiative identified the barriers to solving this complicated problem. Barriers were given hierarchical significance, and solutions and action plans to the barriers were formulated. This article describes the process, the barriers encountered, and the solutions required to fully identify and manage this large and complicated population of patients.

Humans↗
PubMed1987

Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease.

The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated with PKD, c-myc protooncogene expression was studied in a mouse model for autosomal recessive PKD. Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age. Quantitative dot blot and RNA blot hybridization experiments in which whole kidney poly(A)+ RNA was hybridized with a c-myc RNA probe showed a 2- to 6-fold increase in c-myc mRNA at 2 weeks, and a 25- to 30-fold increase in c-myc mRNA at 3 weeks of age in polycystic mice, as compared to normal littermates. c-myc expression was also examined under two conditions in which kidney cell growth was experimentally induced in normal adult mice: compensatory renal hypertrophy and tubule regeneration following folic acid-induced renal cell injury. While compensatory hypertrophy resulted in only a small (less than 3-fold) increase in c-myc, folic acid treatment gave rise after 24 hr to a 12-fold increase in c-myc mRNA. The induction of c-myc by folic acid is consistent with increased cellular proliferation in regenerating tubules. In contrast, polycystic kidneys show only a minimal increase in cellular proliferation over that seen in normal kidneys, while c-myc levels were found to be markedly elevated. Thus, the level of c-myc expression in cystic kidneys appears to be out of proportion to the rate of cell division, suggesting that elevated and potentially abnormal c-myc expression may be involved in the pathogenesis of PKD.

Age Factors↗
PubMed2006

Hypertension and kidney disease: a deadly connection.

Kidney disease may be the cause or a consequence of hypertension. Hypertension affects 25% of the adult population in the United States. Similarly, chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been steadily increasing in incidence because of the increasing age of the US population and rise in the incidence of risk factors, including hypertension. Substantial evidence supports the notion that elevated blood pressure is the most significant risk factor for the development of CKD. Microalbuminuria has been shown to be the early marker of hypertensive renal disease. Furthermore, therapy to reduce microalbuminuria was associated with delay in the progression of renal disease. Black Americans are at higher risk for developing hypertensive nephrosclerosis than whites. Hypertension is a major risk factor for cardiovascular events in patients with CKD and ESRD and those who have undergone renal transplantation. Studies have documented that elevated serum creatinine and CKD are risk factors for a cardiovascular event. Tight blood pressure control has been shown to reduce microalbuminuria and proteinuria and to delay progression of renal disease. Tailoring the choice of antihypertensive medication to the clinical setting to achieve a blood pressure goal is critical in reducing complications from this deadly connection.

Black or African American↗
PubMed1990

The diagnosis and prognosis of autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS: In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.

Adult↗
PubMed1980

Diverticular disease in patients with chronic renal failure due to polycystic kidney disease.

Twelve patients with chronic renal failure and polycystic kidney disease represent 8% of the 151 hemodialysis patients followed up at the Chromalloy American Kidney Center, Washington University School of Medicine. Ten (83%) of these patients have diverticulosis, and four of these patients developed gross colonic perforation secondary to diverticulitis. Barium enemas on 31 chronic renal failure patients without polycystic kidney disease revealed diverticulosis in 10 (32%). None had diverticulitis. Barium enemas in 120 age-matched non-renal failure control patients revealed diverticulosis in 45 (38%). None had diverticulitis. These findings suggest that patients with chronic renal failure due to polycystic kidney disease have a high incidence of diverticulosis and diverticulitis, that diverticulosis occurs in patients with chronic renal failure without polycystic kidney disease at a rate similar to that in the general population, and that diverticulitis should be an initial consideration in the differential diagnosis of abdominal pain in patients with polycystic kidney disease.

Adult↗
PubMed2000

Bilateral nephrectomy with concomitant renal graft transplantation for autosomal dominant polycystic kidney disease.

PURPOSE: There has been controversy about pre-transplant nephrectomy in patients with autosomal dominant polycystic kidney disease. Kidneys may be removed in these patients when they cause respiratory compromise, early satiety, increased abdominal girth, pain, hematuria or recurrent infection. We determined whether concomitant bilateral nephrectomy at renal transplantation is safe and efficacious. MATERIALS AND METHODS: Between December 1996 and January 1999, 10 patients with autosomal dominant polycystic kidney disease underwent bilateral nephrectomy with concomitant renal grafting (group 1). We compared these patients to 9 with autosomal dominant polycystic kidney disease matched for age and gender who underwent transplantation only (group 2) and 4 with the same condition who underwent bilateral nephrectomy and renal transplantation as staged procedures (group 3). RESULTS: No patients died perioperatively. There was a lower rate of complications in group 1 than in groups 2 or 3. The only significant differences in intraoperative and perioperative parameters were operative time and intraoperative blood loss, which were greater in group 1 than in group 2. We noted no significant differences in groups 1 and 3. Patient satisfaction analyzed by a survey revealed that the 70% of group 1 patients who responded were satisfied with kidney removal and 7 of the 9 in group 2 desired native kidney removal. All group 3 patients already had a functioning renal graft but were satisfied with native kidney removal, although they would rather have undergone bilateral nephrectomy at transplantation. CONCLUSIONS: Our data imply that there is no higher morbidity or mortality when performing concomitant bilateral nephrectomy at renal transplantation in patients with renal failure due to autosomal dominant polycystic kidney disease. There was a higher rate of satisfaction in patients who underwent nephrectomy and transplantation simultaneously, while those who did not undergo concomitant procedures strongly desired to have had that option. Bilateral nephrectomy may alleviate symptoms while providing greater room for renal graft placement. When done without transplantation, bilateral nephrectomy resulted in the highest number of complications. Our data indicate that if bilateral nephrectomy is performed as an adjunct to transplantation, it should be done at renal grafting.

Adult↗
PubMed2003

National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Cardiovascular Diseases↗
PubMed2003

The expression of immune-regulatory genes in rainbow trout, Oncorhynchus mykiss, during a natural outbreak of proliferative kidney disease (PKD).

Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by an apparently abnormal immune response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In order to examine the nature of the immune response at the molecular level, the expression of a range of immune regulatory genes, including cytokines and cyclooxygenase (COX)-2 was examined in naive unexposed fish and in naive fish exposed to parasite-infected water at three points during the course of a natural outbreak of PKD. Since fish with advanced PKD pathology generally exhibit increased susceptibility to secondary infections which is typical of stress/cortisol-mediated immune suppression, a further aim of this work was to examine in vitro the influence of the glucocorticoid cortisol on the bacterial lipopolysaccharide (LPS)-induced expression of the trout cytokine genes studied. Two weeks after the initial sampling, naive exposed fish showed a specific profile of up-regulated tumor necrosis factor (TNF)-alpha2, COX-2 and, to a lesser extent, transforming growth factor (TGF)-beta1 expression. As the disease pathology increased, TNF-alpha2 and COX-2 expression returned to normal levels. Stress levels of cortisol suppressed the LPS inducibility of pro-inflammatory cytokine genes, although TGF-beta1 and TNF-alpha2 appeared to be refractory. These data demonstrate that specific immune responses at the molecular level are affected during PKD infection, with the cortisol suppression of cytokine expression in vitro providing a possible link to PKD-mediated cytokine down-regulation and immune suppression.

Animals↗
PubMed2007

Use of do-not-resuscitate orders in patients with kidney disease hospitalized with acute myocardial infarction.

BACKGROUND: Patients with kidney disease are at increased risk for adverse health outcomes in comparison to patients without kidney disease. Therefore, patients with kidney disease may have greater use of do-not-resuscitate (DNR) orders than patients without kidney disease in the setting of an acute illness. We examined the association between advanced kidney disease and use of DNR orders in patients admitted with an acute myocardial infarction (AMI) to all greater Worcester, MA, hospitals as part of an epidemiological study. METHODS: Use of DNR orders in 4,033 Worcester residents hospitalized with AMI at 11 greater Worcester medical centers during 1997, 1999, 2001, and 2003 was examined. Advanced kidney disease was defined on the basis of serum creatinine level at the time of hospital admission. RESULTS: Forty-nine percent of patients with kidney disease and AMI had a DNR order in their medical records compared with 21% of patients without kidney disease. After controlling for a variety of potentially confounding factors, patients with kidney disease were more likely to have a DNR order than patients without kidney disease (adjusted odds ratio, 1.55; 95% confidence interval, 1.21 to 1.98). Patients with advanced kidney disease who received DNR orders were older, had more comorbid conditions, and were at greater risk for dying than patients with kidney disease without a DNR order. CONCLUSION: Advanced kidney disease is associated with greater rates of DNR orders in patients hospitalized with AMI. Awareness of kidney disease may be an important consideration for patients and health care providers in discussing the use of DNR measures.

Aged↗
PubMed2006

Genetic aspects of hyperhomocysteinemia in chronic kidney disease.

Patients with chronic kidney disease who are on dialysis or with a kidney transplant have higher total plasma homocysteine concentrations than individuals who are free from kidney disease. Several single-nucleotide polymorphisms of genes encoding enzymes that are involved in homocysteine metabolism have been studied in these patients. These polymorphisms are located in genes encoding of 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase, methionine synthase, cystathionine beta-synthase, glutamate carboxy peptidase II, reduced folate carrier 1, and transcobalamin II. Among the single-nucleotide polymorphisms studied, only MTHFR 677C>T was associated consistently with total plasma homocysteine levels, but there currently is no evidence of any association between MTHFR 677C>T genotype and long-term outcomes.

Chronic Disease↗
PubMedDate not supplied

Inheritance of polycystic kidney disease in Persian cats.

Polycystic kidney disease in Persian cats culminates in chronic renal failure after a variable clinical course. An affected 6-year-old Persian cat was used to establish a colony of cats with polycystic kidney disease. In affected cats, cysts could be detected by ultrasonography as early as 7 weeks of age. Absence of cysts on ultrasound examination at 6 months of age was correlated with absence of polycystic kidney disease at necropsy. Both males and females were affected and, of progeny from affected x unaffected crosses, 42% were affected and 58% were unaffected. In affected x affected crosses, 73% of progeny were affected and 27% were unaffected. These results are compatible with autosomal dominant inheritance of this trait. Polycystic kidney disease in Persian cats resembles autosomal dominant polycystic kidney disease (ADPKD) in human beings, and represents a valuable animal model of the human disease.

Animals↗