Risk Factors For Renal Injury Research Articles

Clinical Implications of the Solitary Functioning Kidney

Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progression to CKD. However, challenges remain in distinguishing patients with a high risk for disease progression from those patients without a high risk of disease progression. Although it is hypothesized that glomerular hyperfiltration in the lowered number of nephrons underlies the impaired renal prognosis in the solitary functioning kidney, the high proportion of ipsilateral congenital anomalies of the kidney and urinary tract in these patients may further influence clinical outcome. Pathogenic genetic and environmental factors in renal development have increasingly been identified and may play a crucial role in establishing a correct diagnosis and prognosis for these patients. With fetal ultrasound now enabling prenatal identification of individuals with a solitary functioning kidney, an early evaluation of risk factors for renal injury would allow for differentiation between patients with and without an increased risk for CKD. This review describes the underlying causes and consequences of the solitary functioning kidney from childhood together with its clinical implications. Finally, guidelines for follow-up of solitary functioning kidney patients are recommended.

Risk Factors for Renal Injury in Children With a Solitary Functioning Kidney

The hyperfiltration hypothesis implies that children with a solitary functioning kidney are at risk to develop hypertension, proteinuria, and chronic kidney disease. We sought to determine the presenting age of renal injury and identify risk factors for children with a solitary functioning kidney. We evaluated 407 patients for signs of renal injury, defined as hypertension, proteinuria, an impaired glomerular filtration rate, and/or the use of renoprotective medication. Patients were subdivided on the basis of type of solitary functioning kidney and the presence of ipsilateral congenital anomalies of the kidney and urinary tract (CAKUT). The development of renal injury was analyzed with Kaplan-Meier analysis. Risk factors were identified by using logistic regression models. Renal injury was found in 37% of all children. Development of renal injury increased by presence of ipsilateral CAKUT (odds ratio [OR] 1.66; P = .04) and age (OR 1.09; P < .001). Renal length was inversely associated with the risk to develop renal injury (OR 0.91; P = .04). In all patients, the median time to renal injury was 14.8 years (95% confidence interval 13.7-16.0 years). This was significantly shortened for patients with ipsilateral CAKUT (12.8 years, 95% confidence interval 10.6-15.1 years). Our study determines independent risk factors for renal injury in children with a solitary functioning kidney. Because many children develop renal injury, we emphasize the need for clinical follow-up in these patients starting at birth.

Risk Factors for Renal Injury in Children With a Solitary Functioning Kidney

Risk Factors for Renal Injury in Children With a Solitary Functioning Kidney

Risk Factors for Renal Injury in Children with a Solitary Functioning Kidney

Risk Factors for Renal Injury in Children with a Solitary Functioning Kidney

Risk Factors for Renal Injury in Children With a Solitary Functioning Kidney

Risk Factors for Renal Injury in Children With a Solitary Functioning Kidney

Impaired Fasting Glucose Is Associated With Renal Hyperfiltration in the General Population

OBJECTIVEIncreased glomerular filtration rate (GFR), also called hyperfiltration, is a proposed mechanism for renal injury in diabetes. The causes of hyperfiltration in individuals without diabetes are largely unknown, including the possible role of borderline hyperglycemia. We assessed whether impaired fasting glucose (IFG; 5.6–6.9 mmol/L), elevated HbA1c, or hyperinsulinemia are associated with hyperfiltration in the general middle-aged population.RESEARCH DESIGN AND METHODSA total of 1,560 individuals, aged 50–62 years without diabetes, were included in the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6). GFR was measured as single-sample plasma iohexol clearance. Hyperfiltration was defined as GFR >90th percentile, adjusted for sex, age, weight, height, and use of renin-angiotensin system inhibitors.RESULTSParticipants with IFG had a multivariable-adjusted odds ratio of 1.56 (95% CI 1.07–2.25) for hyperfiltration compared with individuals with normal fasting glucose. Odds ratios (95% CI) of hyperfiltration calculated for a 1-unit increase in fasting plasma glucose (FPG) and HbA1c, after multivariable-adjustment, were 1.97 (1.36–2.85) and 2.23 (1.30–3.86). There was no association between fasting insulin levels and hyperfiltration. A nonlinear association between FPG and GFR was observed (df = 3, P < 0.0001). GFR increased with higher glucose levels, with a steeper slope beginning at FPG ≥5.4 mmol/L.CONCLUSIONSBorderline hyperglycemia was associated with hyperfiltration, whereas hyperinsulinemia was not. Longitudinal studies are needed to investigate whether the hyperfiltration associated with IFG is a risk factor for renal injury in the general population.

Effects of weight loss on renal function in overweight Japanese men

Obesity is known as an independent risk factor for renal injury. Sympathetic nerve activation may have an important role of the pathogenesis of obesity, and hypertension may underpin the development of cardiovascular events. In the present study, we evaluated the effects of weight loss (WL) on renal function, especially focusing on sympathetic nervous activity. In 154 overweight or obese Japanese men (89 normotensive and 65 untreated mild hypertensive subjects), body weight, body mass index (BMI), total body fat mass, blood pressure (BP), serum creatinine, blood urea nitrogen, creatinine clearance (CCr) (calculated with the Cockcroft-Gault equation) and plasma norepinephrine (NE) were measured before and after a 12-month period of WL with a mild caloric-restricted diet and exercise. A significant WL was defined as 10% or more WL compared with the entry period. In total, 97 (63.0%) subjects succeeded in significant (by 14.3%) WL at 12 months, and 57 subjects (37.0%) did not succeed in significant WL but they lost 7.7% weight. At entry, levels of plasma NE, serum creatinine and fat mass were significantly lower and CCr was greater in the group with a significant WL compared with those without WL. BMI, total body fat mass and plasma NE significantly decreased, and CCr increased with WL. At both baseline and at the 12-month period, fat mass and plasma NE negatively correlated with CCr and positively correlated with creatinine at each time point. Changes in fat mass and plasma NE over 12 months correlated with changes in creatinine, and only changes in fat mass negatively correlated with changes in CCr. Basal fat mass and plasma NE correlated positively with serum creatinine at 12 months and negatively with CCr at the same time point. In multiple regression analyses, basal plasma NE and fat mass were significant determinants of serum creatinine levels and CCr at 12 months. In conclusion, WL improved renal function (as evident from measures of creatinine and CCr) in overweight individuals. Basal plasma NE levels and total body fat mass could be predictors for improvement in renal function associated with WL. Suppression of sympathetic nervous activation associated with WL may have a role in the ameliorative effects on renal function.

Analysis of the permanent renal injury risk factors in congenital neuropathic bladder

Analysis of the permanent renal injury risk factors in congenital neuropathic bladder

Smoking as a Risk Factor for Renal Injury in Essential Hypertension

Background: Smoking is an important player in the pathogenesis of hypertensive nephropathy. To shed more light on this issue, we performed a case-control cross-sectional study and stratification analyses to evaluate the influence of smoking on surrogate markers of kidney injury and oxidative stress in patients supposed to have hypertensive nephropathy. The dependence of kidney lesions on the ‘extent’ of smoking was determined as well. Methods: 82 patients with essential hypertension and micro- or macro-albuminuria were recruited. The control group consisted of 41 sex- and age-matched healthy individuals. Urine albumin creatinine ratio and plasma von Willebrand factor activity were analysed as markers of endothelial injury. N-acetyl-β-D-glucosaminidase, transforming growth factor-β1 and 15-isoprostane F_2t urine excretions were regarded as markers of tubular dysfunction, renal fibrosis and oxidative stress, respectively. Patients’ smoking habits were recorded and categorized on the basis of a self-administered questionnaire. Results: In multivariate regression analysis, the independent associations between smoking and urine albumin (p < 0.05; β = 0.27), von Willebrand factor activity (p < 0.05; β = 0.29) and urine isoprostanes (p < 0.05; β = 0.28) were found. When the smokers were stratified according to the number of cigarettes smoked per day and the time from which they started smoking, ‘heavy smokers’ and ‘long-term smokers’ presented with higher albumin excretion and higher von Willebrand factor activity than ‘light smokers’ and ‘short-term smokers’, respectively. The passive smokers had numerically higher albumin excretion and von Willebrand factor activity than nonsmokers. Conclusion: The study showed that smoking induces oxidative stress. Smoking was also found to be a strong predictor for the extent of endothelial injury in patients with hypertensive kidney injury. Subjects who smoke heavily and for a long time, as well as passive smokers, seem to be particularly exposed to endothelial damage.

Renal function in meningomyelocele: risk factors, chronic renal failure, renal replacement therapy and transplantation.

This review is on renal function in patients with spina bifida. Risk factors for renal injury as well specific issues concerning the treatment of chronic renal failure, renal replacement therapy and kidney transplantation are discussed. Relevant work published earlier than 2000 is also considered because of a lack of recent literature. Data from adult and paediatric surveys show renal damage to be the single most prevalent cause of morbidity and mortality; even in children, 30-40% exhibit evidence of renal damage. Additional factors such as chronic infection and stone formation will then render the kidney more vulnerable to progressive loss of renal mass and subsequent chronic renal failure. As in other patients with renal insufficiency, the control of hypertension, preferably with angiotensin-converting enzyme inhibitors, and adequate nutrition are mainstays of nephrological care. The modality of dialysis in these patients is complicated by ventriculoperitoneal shunts or urinary stomata in peritoneal dialysis, or difficult vascular access in haemodialysis. Renal transplantation is now considered the optimal treatment for end-stage renal disease in all age groups. Although more prone to complications, recent data on patients with meningomyelocele or severely abnormal lower urinary tracts demonstrate excellent patient and graft outcomes. The common goal in caring for these patients must be the prevention of progressive renal damage. However, once kidney failure has occurred, good and safe techniques for renal replacement therapy are available to bridge the time to transplantation, which is undoubtedly the best treatment for these patients.

Predisposition of spontaneously hypertensive rats to develop renal injury during nitric oxide synthase inhibition

Chronic nitric oxide (NO) synthase (NOS) inhibition results in renal injury. Hypertension is an important risk factor for renal injury. We studied the influence of preexistent hypertension on the sensitivity for renal injury induced by chronic NOS inhibition in rats. Spontaneously hypertensive (SHR) and normotensive Wistar–Kyoto (WKY) rats were treated with 3, 10, 30 and 100 mg/l Nω-nitro-l-arginine (l-NNA) until death. Systolic blood pressure and proteinuria were measured regularly and compared with time-control measurements in untreated SHR and WKY. In WKY, 3 and 10 mg/l l-NNA did not affect systolic blood pressure, while 30 and 100 mg/l l-NNA resulted in an increase in systolic blood pressure after 12 and 4 weeks, respectively. In contrast in SHR, every dose of l-NNA resulted in an increase in systolic blood pressure after 2 weeks. In WKY, 3 and 10 mg/l l-NNA did not affect proteinuria or survival, while 30 and 100 mg/l l-NNA resulted in an increase in proteinuria after 30 and 9 weeks, and a median survival of 36 and 12 weeks, respectively. In SHR, 3, 10, 30 and 100 mg/l l-NNA resulted in an increase in proteinuria after 30, 12, 3 and 3 weeks, and a median survival of 41, 20, 5 and 3 weeks, respectively. Thus, at every dose of the inhibitor, chronic NOS inhibition resulted in far earlier increases in systolic blood pressure and proteinuria and a marked increase in mortality in SHR as compared to WKY. Indeed, a very low dosage of l-NNA that caused no harm in WKY was followed by marked increases in proteinuria and blood pressure and decreased survival in SHR. Hypertension strongly increases the vulnerability to cardiovascular risk factors that compromise the NO-system.

American Indian heritage and risk factors for renal injury

Little is known about the causes and consequences of renal disease among American Indians in the Great Lakes region of the United States. We examined clinical correlates of albumin/creatinine ratios among 1368 participants in the three tribal communities of the Inter-Tribal Heart Project using univariate and multivariate analysis. Compared to 1086 participants without albuminuria, the 240 with microalbuminuria (30 to 299 mg/g) and the 42 with macroalbuminuria (>300 mg/g) were more likely to report a history of a myocardial infarction (6.4%, 16.0%, and 23.8%, respectively, P < 0.001). Similarly, compared to patients without albuminuria, those with microalbuminuria and macroalbuminuria were more likely to report a history of stroke (2.3%, 8.4% and 26.2%, respectively, P < 0.001). In a multiple linear regression model, independent correlates of albumin excretion (P < 0.05) included: fasting blood sugar, treated diabetes, treated hypertension, higher systolic blood pressure, lower diastolic blood pressure, abnormal electrocardiogram, a history of stroke, the degree of American Indian heritage, and lower household income. Urinary albumin excretion is associated with cardiovascular disease outcomes and risk factors among American Indians of the Great Lakes region. Both heredity and socioeconomic status appear to play a role in the pathogenesis of renal injury in this population.

Studying the causes of kidney disease in humans: A review of methodologic obstacles and possible solutions

Until recently, epidemiology has contributed little to the understanding of kidney disease etiology. In the past, the immediate need for therapy eclipsed the longer-term need to develop preventive strategies. As a result, kidney disease epidemiology lacked sufficient institutional and financial support. These difficulties are being progressively (albeit yet incompletely) resolved. Other obstacles pertained to research methods. The need for large cohort studies to investigate a relatively uncommon outcome can be overcome by the use of alternative study designs, such as nonconcurrent prospective studies or case control studies. Unfortunately, other methodologic obstacles remain. These include (1) lack of sensitive markers of early renal insufficiency for use in general populations, (2) variations in access to end-stage renal disease therapy, (3) uncertainty regarding cause-of-death certification in persons with kidney diseases, (4) ambiguous criteria for diagnosing specific renal diseases, (5) lack of independence between risk factor assessments and kidney disease definition, (6) inconsistent risk factor assessments, and (7) inadequate conceptual models for causation of kidney failure. We suggest a global framework, including (1) defining rigorous diagnostic criteria for renal diseases, (2) conducting etiologic studies of “all-cause” end-stage renal disease, (3) systematically collecting data on risk factors for renal injury, and (5) distinguishing between initiators and promoters of renal insufficiency and between proximate and distal risk factors. These suggestions aim to foster a multidisciplinary debate on etiologic research on renal diseases. Identification of modifiable risk factors may provide a basis for effective preventive interventions.

Risk factors for toxic nephropathies

The best definition of risk factors for renal injury, irrespective of the aetiological agent, comes from observations in patients with acute renal failure. From such observations, two subdivisions have evolved, i.e., acute insults and host risk factors. Acute renal insults include: hypertension, sepsis, use of nephrotoxic drugs (e.g., aminoglycoside antibiotics and contrast media), haemoglobinuria or myoglobinuria, liver disease and extracellular volume depletion. Host risk factors include: advanced age, hypertension, gout and hyperuricaemia, diabetes mellitus, chronic renal failure and use of diuretics. Furthermore, the mechanism of acute renal injury can be correlated with different risk factors: for a tubular toxic agent, acting either directly on the cells or haemodynamically, a dose-dependency is characteristic; while for immunologically mediated injury, genetic predisposition is more important. The identification of risk factors for chronic toxic injury is confounded by the possibilities of multiple episodes of subclinical renal injury, the distinct possibility that a major component of the ageing process may be a loss of renal reserve, and a progressive body burden, of e.g., cadmium, which may deplete intrinsic protective mechanisms. However, clinically relevant risk factors can alert the clinician to exercise additional caution when prescribing medications that are potentially nephrotoxic. Such factors include dehydration, pre-existing renal disease, age, co-existing diseases that cause renal ischaemia, gender, concomitantly administered drugs, and electrolyte abnormalities.

Contrast agents--state of the art.

ABSTRACTThe osrnolality and chemotoxicity aspects of contrast agents are reviewed. The next stop in contrast agent development, non‐ionic dimers, is indicated. A mechanism for chemotoxicity is suggested involving the iodine atoms.The mechanisms possibly involved in major adverse reactions are outlined and it is suggested that new contrast agents should be safer. The cost implications are discussed. Nephrotoxicity is briefly examined and it is shown that dehydration for intravenous urography. which is a risk factor for renal injury, is ineffective and unnecessary. Finally, a rarely discussed form of toxicity. namely contrast enhanced tissue radiation injury, is discussed.