Microalbuminuria In People Research Articles

Correlation of uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine.

To find the correlation of serum uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine. This cross-sectional study was conducted in the Department of Diabetes, Endocrinology and Metabolic diseases, Hayatabad Medical Complex, Peshawar, Pakistan from 1st April, 2022 to 30th September, 2022. Total 160 diabetic patients between the age of 30 and 65 years were enrolled in the study. Type-2 diabetic patients with microalbuminuria between 2.5 and 30 mg/mmol were included. The demographic details of patients were recorded in the questionnaire after taking consent. Fasting Uric acid, lipid profile and glucose along with creatinine and HbA1C were estimated from patient's venous blood samples. Ratio of albumin to creatinine (ACR) in the random spot urine sample was used to detect microalbuminuria. Out of 160 participants enrolled in the study there were 86 (54%) males and 74 (46%) females with the mean age of 50.15 ± 11.1 years and BMI of 20.93 kg/m2. Ninety six (60%) of the patients had Type-2 DM for less than five years, while remaining 64 (40%) were more than five years diabetic. Mean serum uric acid calculated was 6.85±2.06(mg/dl), while microalbuminuria was calculated as 8.02±0.78 (mg/mmol). The Pearson correlation of serum uric acid and microalbuminuria based on sex and age was statistically significant(p<0.05). We found that uric acid level was significantly associated with microalbuminuria in people with Type-2 diabetes with normal serum creatinine. Uric acid level can be a potential screening tool for early detection of DKD.

Cost-effectiveness of population-based screening for microalbuminuria in people with type 2 diabetes mellitus in India.

Patients with diabetes have a higher risk of developing chronic kidney disease (CKD). Early detection of CKD through microalbuminuria screening, followed by treatment, delays the progression of CKD. We evaluated the cost-effectiveness of population-based screening of microalbuminuria among normotensive type 2 diabetes mellitus patients aged >40years compared with no screening scenario using a decision tree combined with the Markov model. We considered two scenarios: Scenario I - dipstick microalbuminuria followed by spot-urine albumin-creatinine ratio (ACR) and serum creatinine in sequence; Scenario II - spot urine ACR plus serum creatinine. A mathematical cohort of the target population was simulated over a lifetime horizon with an annual cycle. Data for the model were obtained from secondary resources. The incremental cost-effectiveness ratios (ICERs) were estimated for screening scenarios compared to nonscreening scenario, along with sensitivity analyses. The discounted ICER per quality-adjusted life years gained for annual microalbuminuria screening in the normotensive diabetic population in India were ₹ 24,114 (US$ 308) and ₹ 13,790 (US$ 176) for scenarios I and II, respectively. Annual screening by scenarios I and II resulted in a reduction of 180 and 193 end-stage renal disease (ESRD) cases per 100,000 population, respectively, resulting in a cost saving of ₹ 12.3 and 13.3 Crore spent on ESRD management over 10years. Both scenarios were also cost-effective even at the screening frequencies of 5 and 10 yearly. Microalbuminuria screening was cost-effective at the threshold of one-time GDP per capita in India.

Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease.

Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015. To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 18 October 2021. We also searched clinical trial registries. Date of the most recent search: 22 August 2021. Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. Seven studies were identified through the searches. Six studies were excluded. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. Overall, the certaintyof the evidence provided in this review was very low, since most risk of bias domains were judged to have either an unclear or a high risk of bias. Because of this, we are uncertain whether captopril makes any difference, in total urinary albumin excretion (at six months) as compared to the placebo group, although it yielded a mean difference of -49.00 (95% confidence interval (CI) -124.10 to 26.10) or in the absolute change score, although it yielded a mean difference of -63.00 (95% CI -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean (standard deviation) of 45 (23) mg/day and the placebo group was noted to increase by 18 (45) mg/day. Serum creatinine and potassium levels were reported constant throughout the study (very low-certainty evidence). The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure (very low-certaintyevidence). Overall, we judged the certaintyof the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certaintyof this evidence to be very low.

Liver fat content is independently associated with microalbuminuria in a normotensive, euglycaemic Chinese population: a community-based, cross-sectional study

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is associated with microalbuminuria (MA) in patients with diabetes/pre-diabetes. Whether this association is mediated by blood glucose and blood pressure (BP) remains unclear. This study...

The relationship between resting heart rate and new-onset microalbuminuria in people with type 2 diabetes: An 8-year follow-up study.

AimsMicroalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new‐onset microalbuminuria in type 2 diabetes.MethodsA total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin‐to‐creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70–74, 75–80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria.ResultsDuring the follow‐up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70–74, 75–80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model).ConclusionsThis prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes.

Panel of novel urine biomarkers for incident microalbuminuria in people with type 2 diabetes mellitus

The need to identify novel biomarkers for early diagnosis and treatment of diabetic nephropathy is widely recognized. However, only a few studies have investigated the association between biomarkers and the onset of albuminuria. In this study, we aimed to investigate a panel of biomarkers suitable for predicting microalbuminuria. Some 346 Japanese people with type 2 diabetes exhibiting normoalbuminuria were studied. The endpoint was defined as the onset of microalbuminuria. Thirty biomarkers were selected from among urinary biomarkers described in previous studies. A panel of biomarkers was selected using least absolute shrinkage and selection operator (LASSO). The prognostic performance of the developed panel was evaluated. During a mean follow-up of 6.2years, 45 people progressed to microalbuminuria. A composite panel of six biomarkers (monocyte chemoattractant protein-1, osteopontin, soluble human tumour necrosis factor receptor-1, tenascin C, vascular endothelial growth factor-A and kidney injury molecule-1) was developed using LASSO. Compared with the basal model comprising estimated GFR and urinary albumin-to-creatinine ratio, addition of these six biomarkers significantly increased the overall C index from 0.773 to 0.824 (P=0.019). Net reclassification improvement and integrated discrimination improvement were estimated to be 0.412 (P=0.049) and 0.040 (P=0.040), respectively. Decision curve analysis also showed that the model with the six novel biomarkers had a better prognostic value for predicting the onset of microalbuminuria. The optimism was moderate or negligible according to measures. The panel consisting of six novel urinary biomarkers effectively predicted incident microalbuminuria in people with type 2 diabetes.

Effect of ramadan fasting on microvascular complications in type1 diabetic patients

Abstract Background Diabetes is a complex, chronic illness requiring continuous medical care with multifactorial risk-reduction strategies beyond glycemic control. Ongoing patient self-management education and support are critical to preventing acute complications and reducing the risk of long-term complications. Significant evidence exists that supports a range of interventions to improve diabetes outcomes. Objective This study aimed to demonstrate the impact of fasting on primarily on ẻGFR &amp; microalbuminuria in people with type 1 diabetes and secondarily on neuropathy &amp; retinopathy. It was conducted on 60 patients with T1DM. All patients underwent full history taking, full clinical examination and biochemical tests including FBG, 2h PPBG, HbA1c, fructosamine, s.creatinine, BUN, uACR, eGFR, fundus examination and DN4 Q. Methods This study was conducted on 60 type 1 diabetic patients with microalbuminuria intending to fast Ramadan. Patients were recruited from internal medicine and diabetes clinics of Ain Shams University. The study performed health education 2 months prior to Ramadan 1438 (2017) with follow up throughout the month and after Ramadan. The patients were on basal-bolus regimen, 36 were on lantus, 17 were on NPH and the remaining 7 patients didnot complete the follow up after Ramadan for family reasons. Results There had been significant difference between pre and post-fasting as regards weight and BMI, and non significant difference regards waist circumference. Also highly significant difference between basal and bolus doses before and during Ramadan. There had been no significant difference between pre and post Ramadan regarding fundus examination, systolic and diastolic blood pressure and a significant difference regarding DN4 Q. Regarding no. of successful fasting days and attacks of hypoglycemia, a significant difference was found. Significant difference in FBS, 2hr PPBG, BUN, s.creatinine, uACR and eGFR, and fructosamine. There was a significant positive correlation between eGFR and height, weight before Ramadan and between eGFR and height, weight after Ramadan, no. of successful fasting days Ramadan 2017. Also a significant negative correlation was shown between eGFR and A / C ratio, Cr, BUN before Ramadan and between éGFR and Cr, BUN after Ramadan. Height, BUN before and after Ramadan and A / C ratio before Ramadan were found to be independent predictors of eGFR. Conclusion Ramadan fasting appears to have significant impact on microvascular complications of type 1 DM patients. These impacts can be attributed to many factors as physical sloth, change of time and pattern of feeding, climate conditions at time of fasting especially hot humid weather predisposing to more frequent dehydration with its sequelae as well as non-compliance of some patients to the proper lifestyle, diet and medications.

OBESITY REMAINS A MAJOR RISK FACTOR ASSOCIATED WITH VASCULAR STIFFENING IN TYPE 2 DIABETES

Objective: Obesity is a modifiable risk factor for cardiovascular disease. Associations between body mass index (BMI) and vascular stiffness have been described previously, and weight loss has been found to improve vascular health. Despite this, obesity remains a major health issue in people with Type 2 diabetes (T2D). Design and method: The Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) study is a prospective stratified clinical trial assessing prediction of progression from normo to microalbuminuria in people with T2D. We measured vascular stiffness in 133 participants (carotid-femoral pulse wave velocity (PWV)) at baseline and end of study (mean follow-up 2.8 years). Results: Participants (age, 62 ± 7 years; 28% female) were characterised by well controlled traditional risk factors: blood pressure 135 ± 13 / 77 ± 9 mmHg; HbA1c, 63 ± 12 mmol/mol; total cholesterol, 4.3 ± 1.1 mmol/L; urinary albumin:creatinine ratio, 6.5 ± 4.6 mg/g; estimated glomerular filtration rate; 87 ± 13 mL/min. Median BMI was 30.7 kg/m2 (range, 20.4 to 48.9 kg/m2). During follow-up PWV remained on average stable (baseline, 9.6 ± 1.6; follow-up, 9.6 ± 1.7 m/s; P = 0.884) although 71 participants experienced an increase and 62 a decrease in PWV. Of all the above baseline parameters only BMI was associated with change in PWV (r = 0.277; P = 0.001), and BMI (median, 29.4 vs 30.5 kg/m2; P = 0.047) was the only significantly different factor (P = 0.010) between the two extreme change in PWV quartiles (−1.5 ± 0.1 vs +1.9 ± 0.3 m/s). We found that obese participants (BMI > 30 kg/m2; n = 75) had greater increase in PWV (+0.26 ± 1.18 vs −0.25 ± 1.37; P = 0.025) than normal and overweight participants (BMI < 30 kg/m2; n = 58). Conclusions: In this cohort with well controlled risk factors there was overall no significant change in PWV during follow-up. Obese people, however, experienced greater PWV progression than normal and overweight individuals. Whilst blood pressure and diabetes control are very good in this cohort, obesity remains a difficult-to-treat risk factor for vascular stiffening. In people at risk of diabetic kidney disease such as participants of the PRIORITY study, weight reduction strategies could help to further improve cardiovascular health.

GW27-e0701 Glycemia-specific Prevalence of Microalbuminuria in People with Prehypertension and Ideal Blood Pressure

GW27-e0701 Glycemia-specific Prevalence of Microalbuminuria in People with Prehypertension and Ideal Blood Pressure

Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease.

Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013. To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015. Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.

Prevalence Of Nocurnal Enuresis and Proteinuria In Children With Sickle Cell Disease and Its Relation To Severity Of Painful Crises

Nocturnal enuresis and albuminuria or proteinuria are markers of renal damage in sickle cell disease (SCD) and commonly develop early on in life. Proteinuria progresses with age, leading to chronic kidney disease in adulthood. The aims of this study were to identify the prevalence of enuresis and albuminuria/proteinuria in paediatric patients with SCD in London and to determine the relationship between these and various demographic and clinical variables. Methods A cross sectional, single centre study was conducted. Questionnaire-based interviews themed on nocturnal enuresis were undertaken for patients between the ages of 6 and 17. Urinalysis was performed for the presence of albuminuria or proteinuria. Hospital patient records were accessed for clinical data. Results A total of 56 patients were recruited to the study, of which 27 (51.8%) were female. Twenty patients (35.7%) had a history of enuresis and met the DSM IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria for nocturnal enuresis compared to 5% prevalence in children in the general population1. There was a statistically significant association between enuresis and age, overactive bladder (OAB) symptoms, sleep-disordered breathing (SDB), painful crises and regular transfusions (Table 1). Fourteen out of 29 patients (48.3%) with OAB symptoms reported nocturnal enuresis compared to six out of 27 patients (22.2%) who did not (p&lt;0.05). Of the patients reporting SDB, 48.6% were enuretic compared to 14.3% who did not (p&lt;0.01). Incidence of painful crises per month was higher for the enuretic group (2.29 vs. 0.88, p&lt;0.05) but the mean number of emergency admissions in the preceding 18 months was similar. Of the 14 regular blood transfusion patients, only one (7.1%) was currently enuretic compared to 14 out of 32 (40.6%) who were not receiving any treatment (p&lt;0.05). Seven patients (13.4%) had albuminuria/proteinuria. (Table 2) There was no difference in albuminuria/proteinuria prevalence between the hydroxycarbamide or blood transfusion group compared to the non-treatment group. There was no difference in HbF percentage, systolic BP, frequency of emergency admissions, painful crises per month, haemoglobin levels and estimated glomerular filtration rates (eGFR) in patients with albuminuria/proteinuria and those without. The prevalence of haematuria increased with age; 6.7% in the 6-9 age category compared to 36.4% in the 16 to 17 age category (p=&lt;0.05). Conclusions Nocturnal enuresis and albuminuria or proteinuria is prevalent at an early age in many children with SCD. Early identification and initiation of treatment such as Angiotensin Converting Enzyme inhibitors2 may delay onset of complications especially alongside beneficial sickle cell treatments such as hydroxycarbamide and regular blood transfusions. Questioning parents on enuresis, OAB and SDB sumptoms and undertaking regular urinalysis on younger age groups is a practical and cost-effective surveillance method.

Evaluation of the effectiveness of diabetic nephropathy stage III in patients with type 2 diabetes mellitus therapy with sulodexide

Introduction. Diabetes mellitus (DM) - takes the main place in the structure of endocrine diseases, and the third after cardiovascular and cancer pathology. In Ukraine 1.2 million of people suffer from diabetes and type 2 diabetes occurs in 85-90% of them. In 2004, 3.4 million of people died from diabetes complications. Diabetic nephropathy (DN) is a serious chronic complication of diabetes that leads to the formation of nodular or diffuse glomerulosclerosis. It is the most frequent cause of terminal chronic renal failure (CRF) in the world, accounting for over 25% of all cases of CRF. The generally accepted classification is Moggensen`s classification (1983, WHO), according to which five stages of diabetic nephropathy are identified, the first two stages of them are preclinical. Leading role in the pathogenesis of DN takes hyperglycemia, which is implemented by the phenomenon of glucosetoxicity. A lot of facts underscore the importance of inflammatory mechanisms triggered by cytokines. There's immune and non-immune theory of DN. The basis of non-immune theory is a violation of the synthesis of glycosaminoglycans (GAGs) that are a major component of the glomerular basement membrane (GMB). GAGs create its negative charge, which prevents the passage through the renal filter small negatively charged molecules, including albumin. In hemodynamic regulation leading role belongs to the renin-angiotensin-aldosterone system (RAAS). The blockade of the RAAS system with ACE inhibitors is the basis of a treatment strategy of DN. All mentioned above became a reason for study of the possibility of a new direction in the treatment of DN using the drug sulodexid, which is a natural mixture of GAGs.Objective of the research. Evaluating the effectiveness of sulodexide therapy of DN stage III in patients with type 2 diabetes.Materials and methods. The patients were divided into 2 groups. Group I consisted of 24 patients aged 40 to 68 years. 5 of them were women and 19 were men. In 20 patients from the group alimentary-constitutional obesity was noted. II group consisted of 11 people: 4 women and 7 men, aged 48 to 68 years, 6 of which were suffering from alimentary-constitutional obesity. Patients received standard treatment of type 2 diabetes and hypertension. In group I, sulodexide (600 LPL units intramuscularly 1 time per day for 10 days) was further included. The research of microalbuminuria (MAU) was conducted on admission and on the 10th day of treatment.Results. The initial values of MAU in 1st group were 92,7 ± 25,2 mcg/min. In the dynamics of monitoring rates decreased to 44,4 ± 9,6 mcg/min. The degree of decrease was 47% (p <0.05). In 2nd Group MAU initial values were 46,7 ± 23,4 mcg/min. In the dynamics of monitoring MAU decreased to 29,5 ± 12,6 mcg/min. Degree of decrease was 27% (p <0.05)Conclusions. 1) In patients with stage III DN with diabetes type 2 by including in the basic therapy of sulodexide level MAU was reliable decreased on 47%, which is on 20% lower than in the comparison group (p <0.05).2) During the research reliable direct dependence of decreased MAU rates with its initial values and degree of obesity was found. It indicates the increase in the effectiveness of the drug at a higher initial level of MAU in people with overweight.

Staging of Chronic Kidney Disease

Awareness of chronic kidney disease (CKD) has increased in part because of the definitions and treatment guidelines set out by Kidney Disease Outcomes Quality Initiative (KDOQI); however, the staging system set forth by these guidelines has led to several problems and unforeseen consequences. Stages 1 and 2 CKD are difficult to determine using the standard Modification of Diet in Renal Disease (MDRD) estimation of GFR, and their clinical significance in the absence of other risk factors is unclear. Just because microalbuminuria in people without diabetes is a cardiovascular risk factor does not make it kidney disease. Most patients who receive a diagnosis of stage 3 CKD (GFR between 30 and 59 ml/min) are elderly people, and the vast majority of these patients will die before they reach ESRD. The staging system needs to be modified to reflect the severity and complications of CKD. It is suggested that stages 1 and 2 be eliminated and stages 3, 4, and 5, be simply termed moderate impairment, severe impairment, and kidney failure, respectively. In addition, age should be a modifying factor, especially in moderate kidney impairment. These changes would allow identification and treatment of clinically relevant disease and avoidance of what can seem exaggerated prevalence estimates.

Drugs and the kidney: more than a question of dose

Drugs and the kidney: more than a question of dose

Cohort Studies

Because of their well-documented advantages, randomized controlled trials (RCTs) represent the gold standard for testing hypotheses in medical research. However, RCTs are not ideal for addressing certain research questions ( e.g. , the risk for renal insufficiency associated with alcohol intake). In addition, conducting a properly designed RCT often requires substantial time and resources. For these reasons, including barriers of cost and need for rapid answers, the majority of clinical research studies in the renal literature use an observational design. Although there clearly is a great need for more RCTs that are conducted in populations with kidney disease, rigorous observational studies are extremely valuable and in many circumstances yield similar results as rigorous RCTs (1). Furthermore, although RCTs are considered the gold standard for examining the efficacy of a therapy, studies of prognosis often are addressed best by cohort studies. In this first of a multipart series dedicated to reviewing clinical research methods in nephrology, after providing a brief overview of observational studies, we focus on one of the major subtypes of observational designs: The cohort study. A glossary of common terms that are used in this and subsequent sections of this series is included in Table 1. Details on other methods ( e.g. , case-control studies, RCTs) will be the subject of future reviews. View this table: Table 1. Glossary The simplest form of observational study is the case report or case series, which describes the clinical course of individuals with a particular condition or diagnosis. Such studies often highlight a single clinical condition and at times even suggest a potential biologic mechanism. In a case series, the clinician gains an appreciation of the breadth of abnormalities ( e.g. , range of proteinuria in patients with HIV-associated nephropathy) that may characterize a single disease process. Although these studies may attempt to identify factors or treatments that …

Nephron Number, Hypertension, Renal Disease, and Renal Failure

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension. The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or multihit models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility. Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the Barker hypothesis, which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9). The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

Microalbuminuria in cats.

Microalbuminuria in cats.

New insights into protein intake and progression of renal disease.

For several decades, dietary protein restriction has been considered as a strategy to slow renal disease progression. Recently, a National Kidney Foundation advisory board incorporated recommendations for supervised low-protein diets into guidelines for the care of non-dialyzed patients with chronic kidney failure. Despite this consensus statement, the clinical utility of dietary modification remains controversial. This article reviews new investigations of protein intake as a mediator of renal function and physiology published since 1 October 2002. Population-level data indicate graded risk for progressive renal functional decline with increasing protein intake among women with mild renal insufficiency, and support a possible association of higher protein consumption with the risk of microalbuminuria in people with concomitant diabetes and hypertension. A link between the quantity of protein intake and the rate of renal deterioration is suggested by preliminary prospective studies among incident peritoneal dialysis patients, renal transplant recipients, and animal models of kidney disease. Varied renal consequences based on protein composition were reported in population-based studies, animal-model experiments, and animal studies of in-utero protein exposure. Clinical trial experience raises concern for the feasibility of dietary interventions in practice. New research supports the view that high-protein diets accelerate renal disease progression, suggests differential consequences based on protein source, and explores risk among defined sub-populations. Topics for future exploration include the renal impact of high-protein weight-loss regimens, implications of dietary protein quantity and type across the stages of chronic kidney disease, and translation of animal studies of prenatal nutrition to humans.

Diabetic nephropathy and end-stage renal failure: the Norwegian story.

Diabetic nephropathy is the most common single cause of end-stage renal failure (ESRF) in the Western world, recorded as the cause of renal failure in up to 40% to 45% of those entering renal replacement therapy (RRT) programs. However, marked differences exist between countries; the percentage of patients entering RRT in Norway because of diabetic nephropathy is 10% of the incident RRT population. The percentage in the United States is approximately 40%; therefore, the purpose of the present study was to compare data from Norway with data from the United States in an attempt to detect factors that might explain some of the differences. To make the comparisons as valid as possible, an attempt has been made to focus on populations of similar genetic make-up. The incidence of type 1 diabetes is a little higher in Norway than in the United States, whereas the prevalence of type 2 diabetes may be twice as high in the United States as in Norway; marked differences in the prevalence of obesity is probably a significant causative factor. There seems to be no striking difference in the prevalence of microalbuminuria in people with diabetes in the two populations, whereas there are insufficient data to compare the prevalence of overt proteinuria. The incidence of patients with a diagnosis of diabetic nephropathy as the cause of ESRF entering RRT in the two study populations showed marked differences; the incidence for 1997 was 8.9/million population in Norway and 113/million population in the United States. The proportion of type 2 diabetes was 46% in Norway and 64% in the US (1997). It is unlikely that the marked difference in incidence of RRT can be explained by differences in type 2 diabetes prevalence alone. The populations may not be directly comparable, and differences in the size of study populations and in the choice of renal diagnosis in patients with diabetes as a comorbid factor at the beginning of RRT may introduce uncertainties. Further, data on other factors--such as incidence of death before RRT is indicated, quality of care, and health care delivery, expressed as degree of blood pressure and metabolic control--were not available. Differences in acceptance of diabetes patients into RRT programs are not believed to contribute significantly. Norway is seeing a development toward increasing body weight and a change toward a more sedentary lifestyle, together with an increasing prevalence of type 2 diabetes earlier in life than has previously been the case. An increase in diabetic nephropathy and need for RRT because of type 2 diabetes must therefore be expected in Norway. To understand differences and to best design preventive programs, further comparative studies of the two populations seem warranted.

Factors associated with microalbuminuria in Type 1 diabetes mellitus: a cross-sectional study

In order to determine the prevalence of microalbuminuria in people with Type 1 diabetes mellitus (Type 1 DM) and identify factors associated with microalbuminuria, we studied 312 Type 1 DM patients attending in three hospitals in two Spanish regions over 6 months. Clinical characteristics, micro- and macro-vascular complications, blood pressure, 24-h urine albumin excretion, lipid profile, HbA1 c levels, smoking habits, and family history of hypertension and diabetic nephropathy were recorded. Univariate analysis and multiple logistic regression were used to examine associations between these variables and the prevalence of microalbuminuria. We detected microalbuminuria in 29% of the patients. The prevalence of microalbuminuria was high during the second decade of diabetes and declined thereafter. Univariate analysis showed dyslipidaemia ( P<0.002), previously diagnosed hypertension ( P<0.001), family history of hypertension (sibling alone P<0.006; mother alone P<0.05), family history of diabetic nephropathy ( P<0.001), and laser-treated retinopathy ( P<0.03) to be factors associated with the presence of microalbuminuria. Multiple logistic regression revealed an association between microalbuminuria and family history of nephropathy (OR 7.6, 3.6–16). In conclusion, in our sample the frequency of microalbuminuria seems to be related to the presence of dyslipidaemia, hypertension, and to a family history of hypertension or nephropathy.