Various Stages Of Chronic Kidney Disease Research Articles

Prevention of Chronic kidney disease (CKD) in children

CKD is recognized worldwide as an important problem in children. The overt stage of CKD is end-stage renal disease, which is merely the tip of the iceberg of a large number of “covert less severe diseases. CKD represents a developing process that is initiated by various causes, all with the common end result of persistent and usually progressive damage of varying severity to the kidneys. It is characterized by the common histopathological end point of glomerulosclerosis, tubulointerstitial fibrosis and tubular atrophy, irrespective of the underlying etiology of kidney disease. The aim of the presentation is to identify the clinical and pathological conditions that cause renal damage and suggest measures for its prevention. CKD is defined by the following criteria: a) Kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney with or without decreased glomerular filtration rate (GFR) manifested by one or more of the following features: abnormalities in the composition of the blood or urine, abnormalities in imaging tests, abnormalities on kidney biopsy; b) GFR <60 ml/min/1.73 m2 for ≥3 months with or without the other above-mentioned signs of kidney damage. CKD has been classified into five stages for the purpose of prevention, early identification of renal damage and institution of preventative measures for progression of primary damage and appropriate guidelines for instituting management for prevention of complications in severe CKD [1]. Pediatricians have the opportunity to screen at-risk patients, identify affected patients, prevent renal damage and ameliorate the impact of CKD by initiating early therapy and monitoring disease progression. The prevention of CKD constitutes three important aspects. Primary prevention aims to eliminate or reduce exposure to factors that cause renal disease. Secondary prevention in which the prevention of the progression of renal damage from stage 1 to stage 5 is carried out by introducing appropriate measures at various stages of CKD. Tertiary prevention strategies are focussed on the reduction or delay of long-term complications, impairments or disabilities in established disease, requiring renal replacement therapy (RRT). Meanwhile, in adults, the primary preventative measures are limited to few conditions, such as diabetes mellitus, atherosclerosis and hypertension, in children there is a wide range of conditions that can start even before birth; if not recognized earlier, these conditions can cause renal damage and progress to CKD in childhood, adolescence or later in the adult life.

Urinary ACE2 is associated with urinary L-FABP and albuminuria in patients with chronic kidney disease

Aim. Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme since it converts angiotensin (Ang) II to Ang-(1–7). In addition, ACE2 has been detected in urine from patients with chronic kidney disease (CKD). The aim of this study was to determine the urinary ACE2 levels in patients with various stages of CKD and to identify the factors associated with the presence of ACE2. Methods. We assessed 152 patients with CKD stage G1–G4. The patients were classified according to the presence or absence of diabetes mellitus (DM) (DM group, n = 72; non-DM group, n = 80) and according to the estimated glomerular filtration rate (CKD stage G1/2 group, n = 40; CKD stage G3 group, n = 74; and CKD stage G4 group, n = 38). Parameters were urinary ACE2, urinary albumin/ creatinine ratio (UACR), urinary liver-type fatty acid binding protein (L-FABP), estimated glomerular filtration rate, and other factors determined to be associated with elevated urinary ACE2. Results. Urinary ACE2 was significantly higher in patients with diabetes (p = 0.01) and in patients with CKD stage G4 compared with stages G1–G3 (p < 0.0001). Multivariable regression analysis revealed that urinary L-FABP and UACR were significantly associated with urinary ACE2 levels, indicating that urinary ACE2 is increased in patients with diabetes and advanced stage CKD. Conclusion. ACE2 might continuously protect from both glomerular and tubulointerstitial injury during CKD progression. Taken together, urinary ACE2 might be a marker of kidney renin-angiotensin system activation in such patients.

PUK9 - “Cost Of Illness” Analysis Of Chronic Kidney Disease In The Entire Population Of The Russian Federation

To conduct the “cost of illness” analysis of chronic kidney disease (CKD) based on the entire population of the Russian Federation. Information retrieval was in the public domain. Pharmacoeconomic analysis method “cost of illness” was used. Direct and indirect cost analysis was also performed. Analysis of found epidemiological data revealed that, in fact, in the Russian Federation the only available epidemiological information is on the later stages of CKD (accompanied by the appointment of renal replacement therapy). Based on that during “cost of illness” analysis at the population level we have extrapolated data on the distribution of patients by stage of CKD available in the article Lori A. et al. 2011. Then the cost of various stages of CKD (including direct and indirect costs) per patient was calculated. At the final stage the economic burden of CKD on the entire patient population in the Russian Federation was determined. The total cost for all patients with CKD who are in stages with I to V in the year were: CKD I – 1157758914 $, CKD II – 1348201542 $, CKD III – 2622796532 $, CKD IV – 218480559 $, CKD V (not receiving renal replacement therapy) – 890038600 $, CKD V (on hemodialysis) - 462938674 $, CKD V (on peritoneal dialysis) - 50407252 $, CKD V (exposed of the kidney transplant) - 79916759 $. Thus, the total economic burden of all stages of CKD in country scale was 6830521313 $ per year (1 $ = 66,0983). “Cost of illness” analysis showed the economic burden of CKD on the entire patient population of the Russian Federation and found that the major portion of the cost appears in the early stages of CKD.

Relevance of Insulin Resistance in Chronic Kidney Disease

Introduction and Objectives of the Study: Chronic Kidney Disease (CKD) is a major prevalent disease worldwide associated with low grade systemic inflammation, which predisposes to higher incidence of atherosclerotic complications in CKD. The study is intended to measure Insulin Resistance (IR) in chronic kidney disease and to decipher if there is any relation between IR and various stages of CKD. Methodology: The study population included 45 CKD and 45 healthy controls of either gender. Fasting Blood Sugar (FBS) and Serum Creatinine were measured in the fasting sample collected from both the groups. Estimated Glomerular Filtration Rate (eGFR) was calculated using MDRD formula. The fasting Insulin levels were estimated by Enzyme Linked Immuno Sorbant Assay (ELISA) method and IR was calculated by Homeostasis Model Assessment - Insulin resistance (HOMA IR) index. Regression analysis was used to find out the relationship between IR and other variables. Results: There was a significant increase in fasting insulin levels and IR in CKD cases (4.09±0.83) as compared to controls (0.8±0.2) [p

Deeper insight into chronic kidney disease-related atherosclerosis: comparative proteomic studies of blood plasma using 2DE and mass spectrometry

BackgroundAtherosclerosis is a major cause of cardiac events and mortality in patients suffering from chronic kidney disease (CKD). Moreover, the risk of cardiovascular disease (CVD) development in patients with CKD increases as kidney function declines. Although the close connection between atherosclerosis and kidney dysfunction is undeniable, particular risk factors and specific mechanisms that promote CVD in patients with CKD remain unclear. To gain insight into better recognition of the mechanisms of accelerated atherosclerosis in patients with CKD, we performed a comparative proteomic analysis of blood plasma from patients in various stages of CKD and thus distinct progression of atherosclerosis (n = 90), patients with advanced CVD and normal renal function (n = 30) and healthy volunteers (n = 30).MethodsPlasma samples were depleted using affinity chromatography and divided into three fractions: high-abundant, low-abundant and low-molecular weight proteins. The first two fractions were analyzed by two-dimensional gel electrophoresis and mass spectrometry, the last one has been subjected to direct MS/MS analysis. A proteomic profiles for high-abundant, low-abundant and low-molecular weight proteins fractions were obtained. Differential accumulated proteins were confirmed by selected reaction monitoring analysis (SRM). The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed.ResultsForty-nine proteins (13 high- and 36 low-molecular mass) showed differences in accumulation levels. For eleven of them differential expression were confirmed by selected reaction monitoring analysis. Bioinformatic analysis showed that identified differential proteins were related to three different processes: the blood coagulation cascade, the transport, binding and metabolism of lipoproteins and inflammatory processes.ConclusionsObtained data provide an additional line of evidence that different molecular mechanisms are involved in the development of CKD- and CVD-related atherosclerosis. The abundance of some anti-atherogenic factors revealed in patients with CKD suggests that these factors are not associated with the reduction of atherosclerosis progression in CKD that is typically observed in “classical” CVD. Moreover, obtained data also suggest that mechanism of CVD acceleration may be different in initial and advanced stages of CKD. Undoubtedly, in advanced stages of CKD inflammation is highly pronounced.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0378-8) contains supplementary material, which is available to authorized users.

Nitric oxide status in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular (CVD) morbidity and mortality, mainly due to atherosclerosis. Decreased production or reduced bioavailability of nitric oxide (NO) can result in endothelial dysfunction (ED). Multiple mechanisms are known to cause a state of NO deficiency in patients with CKD. Patients in various stages of CKD grouped as group-1 (CKD stage 1 and 2), group-2 (CKD stage 3 and 4), group-3 (CKD stage 5) and healthy controls were included in the study. Each group of patients and controls comprised 25 subjects. Plasma nitrites, L-arginine, asymmetric dimethyl arginine (ADMA) and citrulline were measured in all the subjects. Patients in all stages of CKD had lower NO and higher ADMA levels compared to controls. Further, group-2 and group-3 patients had lower levels of NO and higher levels of ADMA than group-1 patients. L-arginine levels showed no difference between patients and controls. However, group-3 patients had lower L-arginine levels compared to group-1 patients. Citrulline levels were decreased in group-3 patients. NO production was decreased in patients in all stages of CKD. The decrease could be due to decreased availability of the substrate, L-arginine or due to an increased ADMA, a potent inhibitor of endothelial NO synthase. Therapeutic interventions directed towards improvement of NO production in addition to management of other CVD risk factors may prevent development of ED and facilitate proper management of CKD patients who are at increased risk for CVD.

Nonalcoholic fatty liver disease and the renin-angiotensin system blockers in the patients with chronic kidney disease.

Recent data suggest that the renin-angiotensin-aldosteron system (RAAS) may be of importance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We were interested to investigate whether the therapy with RAAS blockers in patients with different stages of chronic kidney disease (CKD) has any effect on steatosis and fibrosis grade; NAFLD documented by transient elastography (TE) (Fibroscan(®)-CAP). Of 191 patients with various stages of CKD there were 61 patients with CKD grade III and IV, 62 patients with end-stage renal disease treated with chronic hemodialysis and 68 renal transplant recipients. Liver stiffness was selected as the parameter to quantify liver fibrosis. Furthermore, the Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis with the help of TE. CKD patients (p = 0.005) and CKD-NAFLD patients (p = 0.0005) with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) had statistically significant lower degree of liver stiffness in comparison to those without these medications (p = 0.005). Also, we were interested to explore is there any difference in fibrosis and steatosis grade due to use of ACE-I or ARBs. We did not find statistically significant differences between those two subgroups of patients with respect to liver steatosis/fibrosis. Based on our results, RAAS blockers could be an attractive option for the management of NAFLD. We believe that TE provides the opportunity of noninvasive screening of NAFLD in CKD patients. In further prospective analysis, we believe that by using TE as noninvasive method we could investigate are ACE-I/ARBs really effective medications for the treatment of NAFLD in CKD patients.

Association of serum levels of FGF23 and α-Klotho with glomerular filtration rate and proteinuria among cardiac patients.

BackgroundExpression and/or excretion of fibroblast growth factor-23 (FGF23) and its co-receptor Klotho are altered in patients with end-stage renal disease. The possibility that the FGF23/α-Klotho system mediates the aggravated cardiovascular outcome among patients with chronic kidney disease (CKD) has been suggested. We determined whether FGF23 and α-Klotho concentrations are altered among patients with reduced renal function and proteinuria.MethodsSerum FGF23 and α-Klotho were measured in cardiology patients who were not undergoing chronic hemodialysis. Estimated glomerular filtration rate (eGFR) was correlated negatively with FGF23 and positively with α-Klotho.ResultsThe correlation between FGF23 and the renal tubular maximum reabsorption rate of phosphate to the GFR (TmP/GFR) was not significant, but that between FGF23 and serum calcium or inorganic phosphate was significant among patients with an estimated GFR of less than 60 mL/min/m2. By stepwise multivariate regression analysis, eGFR was selected as significant predictor for FGF23 or α-Klotho among patients with an estimated GFR of less than 60 mL/min/m2; however, urine albumin/creatinine ratio was not selected as a predictor for FGF23 or α-Klotho irrespective of the eGFR levels. In patients with eGFR of <60 mL/min/1.73 m2, UACR was significantly associated with log(FGF23); but, this association did not remain statistically significant in a multivariate model.ConclusionsAmong cardiology patients with various stages of CKD, serum concentrations of FGF23 and α-Klotho were associated with renal function, but not with the extent of proteinuria.

Ocular and systemic factors associated with glaucoma in chronic kidney disease patients.

The goal of this study was to examine, the relationship between chronic kidney disease (CKD) and glaucomatous optic disc neuropathy in a cohort of patients from the south-east Serbia and to determine whether limited screening for glaucoma in specific subgroups of patients with CKD is reasonable and justifiable. This cross-sectional study included 328 subjects with various stages of CKD. All patients had visited the Outpatient Department of the Nephrology Clinic, Clinical Center Nis, Serbia. All patients underwent routine ophthalmic examinations. Glaucoma diagnosis based on elevated intraocular pressure (IOP), the presence of excavation of the optic nerve head (C/D ratio), and characteristic glaucomatous visual field loss (MD-mean deviation, PSD-pattern standard deviation). CKD was defined as kidney damage or glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) for >3 months. A total number of 328 CKD patients, 33 (10.1 %) with primary open angle glaucoma and 28 (8.5 %) with ocular hypertension (OH), were included in the study. Patients with CKD and glaucoma had significantly higher mean values of C/D ratio (0.59), visual field mean deviations (dB)-MD (p < 0.001), and visual field pattern standard deviations (dB)-PSD (p < 0.001) than patients with CKD and OH. Stepwise multivariate linear regression analysis confirmed that the most significant factors related to IOP are age (p < 0.05), AHT (p = 0.01), and eGFR (p = 0.001). Multivariate regression analysis also confirmed that the most significant factors related to cup-to-disc ratio are number of years of smoking (p < 0.05), AHT, and sCr (p < 0.01). In conclusion, the prevalence of glaucoma among CKD patients in the cohort from south-east Serbia is 10.1 %. Patients with CKD and glaucoma, eGFR and current cigarette smoking are associated with IOP level, MD, and PSD of visual field and C/D ratio.

Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD.

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) μg/mL and 2.3 (1.7-3.0) μg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.

The Comparison of 24-Hour Urinary Sodium, Albumin, and Protein Excretion in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus Using Insulin Detemir or Insulin Glargine

Insulin detemir induces bodyweight loss or less weight gain in patients with type 2 diabetes mellitus. However, in contrast to insulin detemir, insulin glargine has no weight loss effect. Increased sodium excretion has been speculated to be one of the mechanisms of weight loss by insulin detemir. However, there are no studies in the literature comparing sodium excretion between patients using insulin detemir and those using insulin glargine. There are also no studies comparing the excretion of urinary albumin and urinary protein in chronic kidney disease (CKD) patients using insulin detemir or insulin glargine. Thus, the aim of the current study was to compare the effects of insulin detemir and insulin glargine on sodium, albumin, and protein excretion in patients with various stages of CKD and concomitant type 2 diabetes. Demographic, clinical, and laboratory data were evaluated for all patients. Hypoglycemic attacks, appetite score, 24-h urinary sodium, albumin, and protein excretion were also measured. A total of 47 patients (23 taking insulin detemir, 24 taking insulin glargine) were included in the study. There were no differences with respect to 24-h sodium (p = 0.694), albumin (p = 0.297), or protein excretion (p = 0.202) between patient groups. Appetite and hypoglycemic attacks also did not differ between groups. Use of insulin detemir or insulin glargine was not related to sodium, albumin, and protein excretion in stepwise regression analysis. There was no difference between insulin detemir and insulin glargine with respect to sodium, albumin, and protein excretion in type 2 diabetic CKD patients. Studies are needed both in CKD patients and those with normal renal function to highlight mechanisms regarding the weight loss effect unique to insulin detemir.

Comparative evaluation of oral health status of chronic kidney disease (CKD) patients in various stages and healthy controls

To compare caries, oral hygiene and periodontal status of chronic kidney disease (CKD) patients in different stages and healthy controls. Seventy-four patients diagnosed with CKD and 150 healthy age and sex matched controls were recruited from General Hospital of Udaipur, India. Each subject was examined for caries by decayed, missing and filled teeth (DMFT) index, oral hygiene by simplified oral hygiene index (OHI-S) while gingival and periodontal status were assessed by Loe and Silness gingival and Community Periodontal Index, respectively. All the examinations were conducted by a single investigator. Study subjects presented significantly lower caries experience than the control group but no significant difference was observed among the subjects in various stages of CKD. The mean gingival index score for study group (1.88) was more than twice to that of control subjects (0.92). Stage of kidney disease influenced the gingival and oral hygiene status which decreased as the stage progressed. The overall prevalence of periodontal pockets (70.3%) in diseased subjects was significantly higher than controls (18.9%). More than three quarters (78.9%) of the patients with stage 5 CKD exhibited deep periodontal pockets. Oral hygiene, gingival, and periodontal status decreased as the stage of CKD increased and was worse among study subjects that the controls. Dental caries did not differ significantly with the stage of the renal disease but was significantly lower among study subjects than the controls.

Fibroblast growth factor-23 and calcium phosphate product in young chronic kidney disease patients: a cross-sectional study

BackgroundFibroblast growth factor-23 (FGF-23), a novel marker of bone disease in chronic kidney disease (CKD) has been shown to correlate with vascular calcifications. We aimed to describe the effect of the calcium phosphate product (Ca*P) on FGF-23 concentrations in children and young adults without confounding cardiovascular disease.MethodsPediatric and young adult patients with CKD stages I-V were recruited in this cross sectional study to measure FGF-23, cystatin C, vitamin D-metabolites and other serum markers of bone metabolism. FGF-23 levels were determined with an enzyme-linked immunosorbent assay. The association between FGF-23 and (Ca*P) was assessed using non-parametric methods. Patients were divided into two age groups, less than 13 years of age and greater than 13 years of age.ResultsThis cross-sectional study measured serum FGF-23, in 81 patients (42 females, 51.9%) at London Health Sciences Centre, aged 2 to 25 years, with various stages of CKD (Cystatin C estimated glomerular filtration rate, eGFR=10.7-213.0 ml/min). For the whole entire group of patients, FGF-23 levels were found to correlate significantly with age (Spearman r= 0.26, p=0.0198), Cystatin C eGFR (Spearman r=−0.40 p=0.0002), CKD stage (Spearman r=0.457, p<0.0001), PTH (Spearman r=0.330, p=0.0039), ionized calcium (Spearman r=−0.330, p=0.0049), CysC (Spearman r= 0.404, p=0.0002) and 1,25-dihydroxyvitamin D (Spearman r=−0.345, p=0.0034) concentrations. No significant correlation was found between FGF-23 levels and calcium phosphate product (Spearman r= 0.164, p=0.142). Upon classification of patients into two age groups, less than 13 years of age and more than 13 years of age, correlational results differed significantly. FGF-23 correlated with CysC eGFR( Spearman r= −0.633, p<0.0001), CKD stage (Spearman r=0.731, p<0.0001), phosphate (Spearman r= 0.557, p<0.0001), calcium phosphate product (Spearman r=0.534, p<0.0001), 125(OH)2 Vit D (Spearman r=−0.631, p<0.0001), PTH (Spearman r= 0.475, p=0.0017) and ionized calcium (Spearman r= −0.503, p=0.0015) only in the older group. The relationship between FGF-23 and Ca*P for the older group could be expressed by the exponential model FGF-23= 38.15 e0.4625Ca*P.ConclusionAbnormal values of FGF-23 in adolescents and young adults with CKD correlate with Ca* P in the absence of vascular calcifications, and may serve as a biomarker for the risk of cardiovascular calcifications.

Significance of hypo- and hypernatremia in chronic kidney disease

Both hypo- and hypernatremia are common conditions, especially in hospitalized patients and in patients with various comorbid conditions such as congestive heart failure or liver cirrhosis. Abnormal serum sodium levels have been associated with increased mortality in numerous observational studies. Patients with chronic kidney disease (CKD) represent a group with a high prevalence of comorbid conditions that could predispose to dysnatremias. In addition, the failing kidney is also characterized by a gradual development of hyposthenuria, and even isosthenuria, which results in further predisposition to the development of hypo- and hypernatremia in those with advancing stages of CKD. To date, there has been a paucity of population-wide assessments of the incidence and prevalence of dysnatremias, their clinical characteristics and the outcomes associated with them in patients with various stages of CKD. We review the physiology and pathophysiology of water homeostasis with special emphasis on changes occurring in CKD, the outcomes associated with abnormal serum sodium in patients with normal kidney function and the results of recent studies in patients with various stages of CKD, which indicate a substantial incidence and prevalence and significant adverse outcomes associated with dysnatremias in this patient population.

Impaired GFR is the most important determinant for FGF-23 increase in chronic kidney disease

Objectives It is unclear whether fibroblast growth factor-23 (FGF-23) increases in response to phosphate accumulation or to decrease clearance in chronic kidney disease (CKD) as is the case with other low molecular weight proteins such as cystatin C (CysC). Design and methods This cross-sectional study measured serum FGF-23, CysC, and other serum markers of bone metabolism in 69 patients, aged 18 months–24 years, with various stages of CKD (eGFR = 11–214 mL/min). Results FGF-23 levels were significantly correlated with CysC and parathyroid hormone levels (PTH) on univariate non-linear regression analysis. In multivariate linear regression analysis, log (CysC) ( β = 0.660, p < 0.0001), log (PTH) ( β = 0.038, p = 0.37), and phosphate ( β = 0.222, p = 0.028) explained 69.1% of the variance of FGF-23. Conclusions CysC had the largest unique contribution to FGF-23 variance in this model, supporting the hypothesis that renal clearance may be the most responsible factor for elevated FGF-23 levels in early stages of CKD.

Functional renal reserve capacity in different stages of chronic kidney disease

There is conflict in published reports on the extent of availability of the functional renal reserve (RR) in healthy adults and in various stages of chronic kidney disease (CKD). The aim of the present study was to determine the RR in various stages of CKD. Baseline glomerular filtration rate (GFR) and 'stimulated GFR' following amino acid infusion were measured in 25 volunteers and 100 patients at various stages of CKD by measuring plasma clearance of Tc99m diethyl triamine pentaacetic acid. Any obtained difference between stimulated and basal GFR was considered as RR and expressed as percentage. The mean renal reserve was 23.4% in the healthy control group, 19.08% in CKD stage 1, 15.4% in CKD stage 2, 8.9% in CKD stage 3 and 6.7% in CKD stage 4, respectively. Renal reserve falls relentlessly with progression of CKD from 23.4% in normal to 6.7% in stage 4 CKD. However, RR may also get completely exhausted even with a normal or with a minimal decline basal GFR. Kidneys may retain some RR even up to the GFR level of 15 mL/min.

Editorial: [Statins and Cardiovascular Events in Patients with End-Stage Renal Disease on Hemodialysis. The AURORA Results Suggest the Need for Earlier Intervention

The recently published Assessment of Survival and Cardiovascular Events (AURORA) trial showed that rosuvastatin (10 mg/d) compared with placebo did not result in a significant reduction in vascular events despite a 43% fall in low density lipoprotein cholesterol (LDL-C) levels in patients with end-stage renal disease (ESRD). The reasons for this and previous negative findings are discussed. In contrast, there is evidence that statins exert a nephroprotective action in less advanced chronic kidney disease (CKD). There is need for further trials to establish if patients at various stages of CKD will benefit from statin treatment in terms of both nephroprotection and reduction in vascular events.

Restless legs syndrome in pediatric patients with chronic kidney disease

Sleep disorders have been shown to be more prevalent in adults and children with chronic kidney disease (CKD) and on dialysis. To date, the prevalence and impact of restless legs syndrome (RLS) in various stages of CKD has not been evaluated. The object of this study was to determine the prevalence of RLS in children with CKD in different stages, and to evaluate its impact on sleep and daytime functioning. We conducted a clinic-based or telephone survey of 26 patients in varying stages of CKD to assess for RLS, sleep schedule, and daytime sleepiness. Thirty-five percent of children met criteria for RLS, the majority being in CKD stages 1-4. There were no significant differences seen in sleep schedule and daytime sleepiness between those children with or without RLS. We found that there is an increased prevalence of RLS in children with CKD compared to the general population. This suggests that children with all stages of CKD should be routinely screened for RLS symptoms.

Improvement in eGFR in patients with chronic kidney disease attending a nephrology clinic

The adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR). Between September 1997 and June 2006 1,443 patients (909 male, 534 female) with CKD, with eGFRs ranging from 15 to 89 ml/min, were referred to our nephrology division and categorized using the National Kidney Foundation classification for CKD based on eGFR. The slope of eGFR change (ml/min-1/1.73/m2-1/year-1) was determined by linear regression analysis and the patients were divided into five groups: (1) significantly progressive slope (deterioration) (more negative than -5 ml/min/year); (2) mildly progressive slope (>-5 to <or=-1); (3) stable slope (>-1 to <or=+1); (4) mildly improved slope (>+1 to <or=+5), and (5) significantly improved slope (>or=+5). At the first nephrology referral, 5.8% of the patients were on CKD stage 2 (eGFR: 90-60 ml/m), 46.7% on CKD stage 3 (eGFR: 59-30 ml/m), and 47.5% on CKD stage 4 (eGFR: 29-15 ml/m) CKD. Significantly improved slope was detected in 48.2% of CKD stage 2 patients, 29.3% of CKD stage 3 patients, and only 14.7% of CKD stage 4 patients (P<0.05). Being in stage 4 or stage 3 versus being in stage 2 significantly reduced the likelihood of an improved slope in logistic regression analysis whereas age, gender, presence of hypertension, and diabetes mellitus did not reach the level of significance. Referral to a nephrology clinic can lead not only to arrest of progression of CKD but also to regression/improvement. Early referral is a positive predictive factor for improvement in eGFR, which emphasizes the importance of such referral. The previously held idea that, once established, CKD progresses invariably is not valid anymore.