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A history of diabetes mellitus or how a disease of the kidneys evolved into a kidney disease.

Diabetes mellitus has a long history during which it was considered to be a disease of the kidneys well into the middle of the 19th century. Recognized in antiquity from its excessive urine output and described as a disease of the urinary tract, its clinical features and fatal outcome were quite accurately recorded by the 1st century ad . Galen (129-200) described it as a disease specific to the kidneys because of a weakness in their retentive faculties. The sweet taste of diabetic urine, which is described in ancient Indian texts and noted by Avicenna (980-1037) and Morgagni (1635-1683), was attributed to the passage of absorbed water and nutrients unchanged into the urine. In 1674, Thomas Willis (1621-1675) first differentiated diabetes from other causes of polyuria by the sweet taste (quasi melle) of diabetic urine and suggested that the sweetness first appears in the blood. A century later, Matthew Dobson (1732-1784) showed that the urine sweetness was because of sugar and was preceded and accompanied by sugar in the blood. Although diabetes then came to be ascribed to increased sugar in the blood, the presence of sugar in the urine continued to be attributed to the decreased retentive properties of the kidneys. The experimental production of diabetes in pancreatectomized dogs that could be reversed by subcutaneous pancreatic transplantation in 1889, and ultimate isolation of insulin in 1922 clearly established diabetes as an endocrine disease. The stage of diabetes as a disease of the kidneys was now over but that of diabetes as a cause of kidney disease was yet to come. Diabetes as a cause of end stage kidney disease was first described in 1936 and extensively documented shortly thereafter, whereas the evidence of its increasing prevalence as a cause of chronic kidney disease continues to accrue.

Diabetes Mellitus↗

Increased mean arterial pressure and aldosterone-to-renin ratio in Persian cats with polycystic kidney disease.

Polycystic kidney disease (PKD) in Persian cats has been increasingly reported and compared to human autosomal dominant polycystic kidney disease (ADPKD) in the last decade. In cats, however, few studies have dealt with the occurrence and hormonal determinants of hypertension, one of the most common extrarenal manifestations of ADPKD in humans. The purpose of this study was to compare Persian cats >4 years old with PKD to unaffected control cats with regard to blood pressure (BP), plasma renin activity (PRA), serum aldosterone concentration, plasma atrial natriuretic peptide (ANP) concentration, and aldosterone-to-renin ratio (ARR). Three gender- and age-matched groups were studied, each consisting of 7 cats: (1) a control group without cysts, (2) a group with mild PKD, and (3) a group with severe PKD (multiple cysts and renal enlargement). Mild renal insufficiency was found in only 1 of 14 cats with PKD. Cats with PKD had a higher mean arterial pressure (P = .04) and more often had a high ARR (P = .047) than did control cats. Tendencies toward higher diastolic and systolic arterial pressures (DAPs and SAPs, respectively) and lower PRAs were observed in cats with PKD compared to controls (.05 < P < or = .1). No significant differences were found between the groups in serum aldosterone and plasma ANP concentrations. None of the cats had echocardiographic evidence of cardiac hypertrophy. In conclusion, cats with PKD had a minor increase in mean arterial pressure compared to control cats, and half of the cats had a high ARR.

Aging↗

[Gene diagnosis of autosomal dominant polycystic kidney disease type 2 using microsatellite DNA tightly linked to polycystic kidney disease gene 2].

OBJECTIVE: To use microsatellite DNA tightly linked to polycystic kidney disease gene 2 in the gene diagnosis of autosomal dominant polycystic kidney disease type 2. METHODS: Microsatellite DNA of D4S1534, D4S1542, D4S1563,D4S2460 and D4S423 were amplified with PCR and the fragments of products were analyzed by capillary electrophoresis and Genescan and Genotyper software, and then gene diagnosis of the pedigrees was made by linkage analysis. RESULTS: Three families were found to be linked to PKD2 in 20 families. Two carriers of PKD2 mutation were revealed by linkage analysis. CONCLUSION: Gene diagnosis can be done for PKD2 mutation carriers prior to cytogenesis. Linkage analysis is a rapid, simple method for studying the heterogeneity of polycystic kidney disease and for diagnosing the disease at the molecular level.

Female↗

Evidence for increased cardiovascular disease risk in patients with chronic kidney disease.

PURPOSE OF REVIEW: Chronic kidney disease is becoming recognized as an important risk factor for cardiovascular disease. Recent publications on cardiovascular disease risk in chronic kidney disease, cardiovascular disease risk factors in chronic kidney disease and clinical trials for cardiovascular disease risk reduction in chronic kidney disease are summarized. RECENT FINDINGS: An American Heart Association statement published in 2003 recommended that patients with chronic kidney disease be considered as members of the 'highest risk group' for subsequent cardiovascular disease events. In the past year, several large prospective studies have reported that cardiovascular disease risk is independently associated with chronic kidney disease markers, e.g. elevated serum creatinine, low estimated glomerular filtration rate and microalbuminuria. The populations studied have included community samples of middle-aged and older adults, subjects with myocardial infarction, those undergoing coronary angiography, and transplant patients. There is a very strong crude association between a low glomerular filtration rate and cardiovascular disease and mortality. Much of the association is explained by traditional cardiovascular disease risk factors, but an independent risk remains. Studies have documented a disturbing underutilization of preventive treatments for cardiovascular disease among patients with chronic kidney disease. Studies of non-traditional cardiovascular disease risk factors are reviewed. The utility of targeting these for cardiovascular disease risk reduction needs to be proved. A summary of large ongoing clinical trials intended to reduce cardiovascular disease risk in chronic kidney disease is presented. SUMMARY: Increasing data support the importance of chronic kidney disease as a predictor of cardiovascular disease risk. However, treatments designed to lower cardiovascular disease risk are used less often in patients with chronic kidney disease than in patients without chronic kidney disease. There is a need for increased application and testing of cardiovascular disease prevention treatments in chronic kidney disease.

Aging↗

Diagnosis, pathogenesis, and treatment prospects in cystic kidney disease.

Cystic kidney diseases (CKDs) are a clinically and genetically heterogeneous group of disorders characterized by progressive fibrocystic renal and hepatobiliary changes. Recent findings have proven the cystogenic process to be compatible with cellular dedifferentiation, i. e. increased apoptosis and proliferation rates, altered protein sorting and secretory characteristics, as well as disorganization of the extracellular matrix. Compelling evidence suggests that cilia play a central pathogenic role and most cystic kidney disorders converge into a common pathogenic pathway. Recently, several promising trials have further extended our understanding of the pathophysiology of CKD and may have the potential for rational personalized therapies in future years. This review aims to summarize the current state of knowledge of the structure and function of proteins underlying polycystic kidney disease, to explore the clinical consequences of changes in respective genes, and to discuss potential therapeutic approaches.

Genotype↗

Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

BACKGROUND: Recently developed clinical practice guidelines and calibration of the Third National Health and Nutrition Examination Survey (NHANES III) serum creatinine assay provide a basis for estimating the prevalence and distribution of chronic kidney disease (CKD) in the United States using standardized criteria based on estimated glomerular filtration rate (GFR) and persistent albuminuria. METHODS: A nationally representative sample of 15,625 noninstitutionalized adults aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR), kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine level, spot urine albumin level, age, sex, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation and compared with the Cockcroft-Gault equation for creatinine clearance (CCr). RESULTS: The prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of individuals older than 65 years without hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates, CCr estimates showed a steeper decline with age and were lower in non-Hispanic blacks. CONCLUSION: CKD is common and warrants improved detection and classification using standardized criteria to improve outcomes. Am J Kidney Dis 41:1-12.

Adult↗

Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort.

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by gradual renal enlargement and cyst growth prior to loss of renal function. Standard radiographic imaging has not provided the resolution and accuracy necessary to detect small changes in renal volume or to reliably measure renal cyst volumes. The Consortium for Radiologic Imaging Studies in Polycystic Kidney Disease (CRISP) is longitudinally observing ADPKD individuals using high-resolution magnetic resonance (MR) imaging to determine if change in renal and cyst volumes can be detected over a short period of time, and if they correlate with decline in renal function early in disease. METHODS: Standardization studies were conducted in phantoms and four subjects at each participating clinical center. After, in the full-scale protocol, healthy ADPKD individuals 15 to 45 years old with creatinine clearance>70 mL/min underwent standardized MR renal imaging, renal iothalamate clearance, comprehensive clinical evaluation, and determination of 24-hour urinary albumin and electrolyte excretion. Stereology was used from T1-weighted images to quantify renal volume, and region-growing thresholding was used from T2-weighted images to determine cyst volume. Renal structures were evaluated in relation to demographic, clinical, and biochemical variables using means/medians, standard deviations, and Pearson correlations. RESULTS: Reliability coefficients for MR renal and cyst volume measurements in phantoms were 99.9% and 89.2%, respectively. In the full-scale protocol, 241 ADPKD individuals (145 women and 96 men) were enrolled. Total renal, cyst, and % cyst volume were significantly greater in each decade group. Hypertensive individuals demonstrated greater renal, cyst, and % cyst volume than normotensive subjects. Age-adjusted renal (r = -0.31, P < 0.0001), cyst (r = -0.36, P < 0.0001), and % cyst volume (r = -0.35, P < 0.0001) were inversely related to glomerular filtration rate (GFR). Age-adjusted renal volume (r = 0.42, P < 0.0001), cystic (r = 0.39, P < 0.0001, and % cyst volume (r = 0.41, P < 0.0001) were related with urinary albumin excretion. CONCLUSION: MR measures of renal and cyst volume are reliable and accurate in patients with ADPKD. ADPKD is characterized by significant cystic involvement that increases with age. Structure (renal and cyst volume) and function (GFR) are inversely related and directly related with the presence of hypertension and urinary albumin excretion in individuals with normal renal function.

Adolescent↗

Comparison of methods for determining renal function decline in early autosomal dominant polycystic kidney disease: the consortium of radiologic imaging studies of polycystic kidney disease cohort.

A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance>70 ml/min were followed annually for four visits. Iothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0; 95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (e.g., creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.

Adolescent↗

Outcomes associated with hypogonadism in men with chronic kidney disease.

Chronic kidney disease is commonly accompanied by disturbances in the hypothalamic-pituitary-gonadal axis. Such disturbances in men give rise to hypogonadism and low circulating testosterone levels. The deficiency in testosterone can contribute to clinical outcomes such as sexual dysfunction, decreased bone mineralization, malnutrition and decreased muscle mass, and anemia. The administration of androgens to nonuremic hypogonadal men is usually effective in treating such outcomes. By contrast, the response to therapy in uremic men tends to be much less predictable. This variability in response is not surprising, because these same clinical outcomes can be the result of other aspects of the uremic state or the comorbid conditions that are frequently present in men with chronic kidney disease. Although further studies are needed, testosterone therapy may prove most useful as an adjunct to other more general therapies designed to address the uremic state.

Chronic Disease↗

Cardiovascular disease in chronic kidney disease from a cardiologist's perspective.

PURPOSE OF REVIEW: Cardiovascular disease accounts for the majority of morbidity and mortality in patients with chronic kidney disease (CKD). This review therefore concentrates on CKD from the viewpoint of the cardiologist. RECENT FINDINGS: Studies have identified several explanations for this observation, including high rates of risk factors for cardiovascular disease, lesser use of cardioprotective strategies, adverse outcomes with cardiovascular drugs and procedures, and accelerated atherosclerosis and myocardial disease in CKD. Because recent studies have rigorously controlled for confounding factors, there is an emerging recognition that CKD is an independent cardiovascular risk state. Conversely, CKD appears to be the result of systemic atherosclerosis. The relative under-utilization of cardioprotective therapies has been an increasingly reported finding in the literature. It appears that conventional cardiovascular risk factor reduction in both the chronic and acute care settings has a greater relative benefit in those patients with CKD than in those with normal renal function. SUMMARY: CKD is an independent cardiovascular risk state. Hence, there is a strong rationale for research in CKD patients into the pathogenesis of CVD. In addition, there are multiple opportunities for improving cardiovascular outcomes in patients with CKD, including both chronic and acute cardiovascular risk reduction.

Cardiovascular Diseases↗

[Glomerular changes in interstitial kidney diseases].

49 kidney specimens of patients with primary interstitial kidney disease (hydronephrosis in 12, tubulo-interstitial nephritis in 13, analgesic nephropathy in 10, adult polycystic renal disease in 9, oxalosis in 4, and renal dysplasia in 1) were examined for glomerular lesions. Light microscopic investigation showed severe focally and segmentally accentuated glomerular changes in 13 cases (27%). Lesions resembling focal sclerosis were found in 11 cases and focal-segmental mesangial proliferation in 2 cases. The results reveal that glomerular lesions occur frequently in primary interstitial kidney disease and can be found in all of the above-mentioned diagnostic entities.

Adolescent↗

[Cystic kidneys (autosomal dominant polycystic kidney disease)].

Polycystic kidney disease is a rather common genetic disorder, with an estimated amount of 8 to 10% of patients in the dialysis population. Meanwhile the defective gene of autosomal dominant polycystic kidney disease [ADPKD], another common terminus for this disorder, has been localized on the short arm of chromosome 16. The genetic disorder is not strictly localized on the kidney, whereas other organ systems like cardiac valves, brain arteries, liver, colon, etc. may be involved in the disease process. Hypertension is an early and common feature of the disease and its probably an important factor for progression of renal failure in ADPKD. Not all carriers of the ADPKD-trait progress to endstage renal failure, about 50% at the age of 50 years. Patients with ADPKD have a good prognosis in renal replacement therapy programs such as dialysis or renal transplantation.

Adolescent↗

Polycystic kidney disease. Morphological diagnosis of recessive and dominant polycystic kidney disease in infancy and childhood.

Histological findings in 75 children with polycystic kidney disease were analysed. The patients had been divided into recessive (RPKD), dominant (DPKD), and sporadic cases on the basis of family investigations. The histological findings in the patients with RPKD and DPKD were compared with each other in order to define criteria for classification of the sporadic patients. The kidneys of the neonatally-deceased patients with RPKD (26 patients) and DPKD (4 patients) were macroscopically very similar. On histological investigation, all patients with RPKD (32 patients) showed cysts derived from the collecting ducts. In DPKD, the cyst epithelium was more variable, and the presence of glomerular cysts served as a useful histological marker of this disorder. In RPKD there was diffuse biliary dysgenesis, in contrast to the normal liver in the neonatally-deceased DPKD patients. However, one DPKD patient who survived also had biliary dysgenesis. Using the observed differences between RPKD and DPKD as criteria, all sporadic patients with satisfactory histological material could be classified as RPKD. We conclude that the differential diagnosis between RPKD and DPKD can be based on kidney and liver histology.

Adolescent↗

Efficacy of taxol in the orpk mouse model of polycystic kidney disease.

Polycystic kidney disease (PKD) a is common disease in the human population that can lead to renal failure and death. Taxol has recently been reported to be of therapeutic benefit in the cpk mouse model of PKD. To determine whether these results also apply to other models of PKD, we studied the effects of taxol treatment on the development of renal cysts and biliary hyperplasia/dysplasia/fibrosis in the orpk mouse mutant, a unique murine model for human autosomal recessive PKD. We report no significant differences between the treatment and control groups with respect to weight gain, survival, urine to serum osmolality ratio, and serum concentration of liver enzymes. Moreover, renal cystic development was not affected by taxol treatment in the orpk mutant animals. This was confirmed by lectin staining and morphometric analysis of the renal cysts, which indicated no significant differences between treatment groups. Therefore, while taxol has a positive effect on the cystic kidney disease in cpk mutant mice, this effect is not applicable to all forms of PKD.

Aging↗

No disease-associated mutations found in the coding sequence of the canine polycystic kidney disease gene 1 in Bull Terriers with polycystic kidney disease.

The aim of this study was to identify possible disease-associated mutations in the canine homologue of the polycystic kidney disease gene 1 (PKD1) in Bull Terriers with autosomal dominant polycystic kidney disease. Messenger RNA was obtained from the blood or renal tissue of five Bull Terriers with the disease and four close relatives without the disease. Reverse transcription, PCR and 3' rapid amplification of cDNA ends were used to amplify the coding and 3' untranslated regions of this transcript. Comparison of PKD1 sequence between the affected and unaffected Bull Terriers, revealed six polymorphisms, but no disease-associated mutations.

Animals↗

Moyamoya disease associated with polycystic kidney disease and eosinophilic granuloma.

Moyamoya disease has been associated with renal artery stenosis, cerebral hemorrhage, and multiple cranial traumas. We report a unique case of moyamoya disease associated with polycystic kidney disease and eosinophilic granuloma. Although the etiology of moyamoya disease is unknown, a familial pattern of occurrence has been documented. Of particular importance is its presentation with polycystic kidney disease, an autosomal dominant disease, suggesting a hereditary component to the etiology of this unusual vasculitic disease.

Adult↗

Management of pediatric patients with chronic kidney disease.

Chronic kidney disease in children is associated with complications that require nursing interventions in both the inpatient and outpatient settings. Given the progressive nature of the disease and the complexity of the treatment regimen, it is important that nurses be comfortable implementing acute and preventive care strategies and facilitating the coordination of care. In addition, the need for multiple therapies can be distressing for patients and theirfamilies, further supporting the role of the nurse in patient and family education and decision making regarding the plan of care. In this review, we discuss the pertinent issues of pediatric chronic kidney disease in the context of a case study to promote better understanding of real-world nursing practice.

Anemia↗