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Atherosclerotic damage to the kidney is one of the most prevalent causes of chronic kidney disease and ultimately kidney failure. It frequently coincides with atherosclerotic damage to the heart, the brain and the lower extremities. In fact, the severity of the damage in the various end organs runs in parallel. As damage to the kidney is easy to measure by monitoring albuminuria and eGFR, and as the early phases of kidney damage frequently precede the alarming symptomatology in the heart, brain and peripheral vasculature, we argue that the nephrologist should consider taking the lead in better organizing early detection and management of CKD. The nephrologist can guide the general practitioner and general health care workers to offer better preventive care to the subjects at risk of progressive atherosclerotic end-organ damage. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is common and associated with significant morbidity. Given the high risk of cardiovascular morbidity and mortality in patients with chronic kidney disease, it is important to identify and treat related risk factors. However, there is growing uncertainty about the benefits of some recommended treatment targets. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines recommend an A1C level of less than 7 percent in patients with diabetes mellitus, although there is no evidence that treatment to this goal reduces cardiovascular events or progression to end-stage renal disease. Optimal blood pressure goals are controversial, and further study is needed to determine these goals in relation to amount of proteinuria. Concurrent use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers leads to worsening kidney function and is not recommended. Lipid-lowering therapy has been shown to reduce the risk of cardiovascular events and mortality, but not progression of chronic kidney disease. The treatment of anemia in patients with chronic kidney disease, particularly the use of erythropoiesis-stimulating agents and optimal hemoglobin goals, is also controversial. Studies have shown increased morbidity and mortality with use of erythropoiesis-stimulating agents aimed at normalizing hemoglobin levels. Patients with chronic kidney disease are at high risk of morbidity and mortality from the use of intravenous contrast agents. Isotonic intravenous hydration with sodium bicarbonate or saline has been shown to prevent contrast-induced nephropathy. Gadolinium-based contrast agents should be avoided if the glomerular filtration rate is less than 30 mL per minute per 1.73 m² because of the risk of nephrogenic systemic fibrosis. [ABSTRACT FROM AUTHOR]

Objectives Many chronic kidney disease (CKD) patients have persistent overt proteinuria despite angiotensin receptor blocker (ARB) treatment. This study investigated whether the initial difference in intrarenal renineangiotensin system activity measured with urinary angiotensinogen would affect the antiproteinuric effects of ARB. Methods Between September 2005 and September 2008, in 50 non-diabetic proteinuric CKD patients not taking renineangiotensin system inhibitors, the urinary protein/creatinine ratio (P/Cr), angiotensinogen/creatinine ratio (AGT/Cr), plasma renin and aldosterone were measured before starting valsartan, and were followed for 18 months. Results Patients were divided into three groups according to their initial urinary AGT/Cr. The urinary P/Cr was lower in the low angiotensinogen group, but similar in the high and extremely high angiotensinogen groups (1.3±0.38 vs 2.0±0.92 vs 2.2±0.78). In all groups, the urinary P/Cr was decreased most for the first 6 months. The urinary P/Cr reduction at 6 months was greatest in the high angiotensinogen group (-24.2% vs -46.2% vs -16.4%). The urinary AGT/Cr was decreased most in the high angiotensinogen group. Renal functional deterioration was attenuated in the high angiotensinogen group compared with the extremely high angiotensinogen group. Conclusions The antiproteinuric effects of ARB were different according to the initial urinary angiotensinogen levels. These results suggest the potential value of the initial urinary AGT/Cr for predicting the therapeutic effect of ARB in proteinuric non-diabetic CKD patients. [ABSTRACT FROM AUTHOR]

Background. Many physicians retain reservations regarding the routine prescription of renin–angiotensin blockade (RAB) in patients with atheromatous renovascular disease (ARVD). Conversely, these patients are in most need of the cardio- and renal protection offered by RAB. This reservation is mostly because of fear of precipitating acute renal deterioration. We aimed to study whether RAB can be used safely in ARVD patients and whether it altered their outcome. Methods. Prospective observational study of all ARVD patients presenting to our tertiary referral centre from 1999–2009. Data capture included usage and tolerability of RAB, and correlation with endpoints of cardiovascular events, dialysis or death. Results. Six hundred and twenty-one subjects were available for analysis. Mean age (SD) of the cohort was 71.3 (8.8) years, median (interquartile range) follow-up 3.1 (2.1, 4.8), range 0.2–10.61 years. Seventy-four patients had an intolerance to RAB at study entry. When utilized prospectively, RAB was tolerated in 357 of 378 patients (92%), and this was even seen in 54/69 (78.3%) patients with bilateral >60% renal artery stenosis (RAS) or occlusion. Patients (4/21) who were intolerant of RAB during follow-up (and 12 retrospectively intolerant), underwent renal revascularization which facilitated safe use of these medications post-procedure. On multivariate time-adjusted analysis, patients receiving RAB were significantly less likely to die (P = 0.02). Conclusion. RAB is well tolerated even in patients with bilateral severe RAS and reduced mortality in a large group of ARVD patients. We recommend all ARVD patients be considered for RAB therapy unless an absolute contra-indication exists. Intolerance of these agents due to renal dysfunction should be considered an emerging indication for renal revascularization to facilitate their re-introduction. [ABSTRACT FROM PUBLISHER]

In the present study, we tested the hypothesis that up-titrating the dose of an angiotensin receptor blocker (ARB) is superior to combined treatment with an ARB and a calcium channel blocker for the same degree of blood pressure (BP) reduction, with respect to urinary albumin excretion in diabetic patients treated with a standard dose of the ARB. Hypertensive patients with type 2 diabetes mellitus and albuminuria (30 mg g−1 creatinine) were enroled in the study, and were either started on or switched to candesartan (8 mg per day) monotherapy. After a 12-week run-in period, baseline evaluations were performed and patients with BP 130/80 mm Hg were randomly assigned to receive either candesartan (12 mg per day) or candesartan (8 mg per day) plus amlodipine (2.5 mg per day) for a further 12 weeks. The primary end-point was a reduction in urinary albumin levels. Although there was no significant difference in the BP reduction between the two groups, the reduction in urinary albumin was greater in the up-titrated than the combination therapy group (−40±14% vs −9±38%, respectively; P<0.0001). Thus, up-titration of candesartan more effectively reduces urinary albumin excretion than combined candesartan plus amlodipine in hypertensive patients with diabetes for the same degree of BP reduction. [ABSTRACT FROM AUTHOR]

Background: Klotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD).Methods: The levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system. Results: The amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r = 0.407, p < 0.01) and the serum Klotho levels (r = 0.232, p < 0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r = 0.834, p < 0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r = 0.726, p < 0.01). Conclusions: The amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully. [ABSTRACT FROM AUTHOR]

Background: A number of studies during the nineties have shown that antihypertensive therapy, particularly using RAS blockade, can reduce uremia progression, and ESRD incidence. Methods: National incidence rates were studied of end stage renal disease (ESRD) for Denmark between 1990 and 2011, and of national prescription of antihypertensive drugs between 1995 and 2010, in order to investigate whether prescription rates had changed, and whether the expected change in ESRD had materialized. The Danish Nephrology Registry (DNR) is incident and comprehensive. Incidence rates were classified according to renal diagnosis. Results: ESRD incidence was constant for age groups <60 years. Incidence rates rose during the nineties for all cohorts >60 years. Since 2001 rates for subjects 60-70 years have fallen from 400 ppm/yr to 234, and since 2002 for subjects 70-80 years from 592 to 398. The incidence of patients >80 years has increased to 341. The falling incidence for patients 60-80 years was distributed among a number of diagnoses. Since 1995 national antihypertensive drug therapy has increased from 24.5 defined daily doses (DDD)/citizen/yr to 101.3, and the proportion using renin-angiotensin system (RAS) blockade from 34 to 58%. Conclusions: This national study has shown a reduction in actively treated ESRD incidence among patients aged 60-80 years. It is possible that this is the result of increased antihypertensive prescription rates, particularly with RAS blockade. If it is assumed that therapeutic intervention is the cause of the observed reduced incidence, ESRD incidence has been reduced by 33.8 ppm/yr, prevalence by 121 ppm, and ESRD expenditure by 6 €/citizen/yr. [ABSTRACT FROM AUTHOR]

Background: The vitamin D receptor activator paricalcitol has been shown to reduce albuminuria. Whether this is a unique property of paricalcitol, or common to all vitamin D analogues, is unknown. The primary aim of this study was to evaluate the effect of alfacalcidol on proteinuria, measured as 24 hour (24 h) albuminuria, in patients with chronic kidney disease (CKD) stage 4-5 being treated for secondary hyperparathyroidism (sHPT). Methods: A retrospective single-center study including adult patients with CKD 4-5, undergoing treatment for sHPT with alfacalcidol, with macroalbuminuria in minimum one 24 h urine collection. Patients were identified in a prospectively collected database of all patients with S-creatinine > 300 µM or creatinine clearance < 30 ml/min. The observation period was from 1st of January 2005 to 31st of December 2009. Phosphate binders and alfacalcidol were provided to patients free of charge. Results: A total of 146 macroalbuminuric patients were identified, and of these, 59 started alfacalcidol treatment during the observation period. A 12% reduction in 24 h albuminuria was seen after starting treatment. In 19 patients with no change in renin-angiotensin-aldosteron-system (RAAS) inhibition, the reduction in albuminuria was 16%. The reduction remained stable over time (9%) in a subgroup of patients (n = 20) with several urine collections before and after the start of alfacalcidol-treatment. Conclusion: The present study supports experimental and clinical data on antiproteinuric actions of activated vitamin D analogues, and suggests that this may be a class-effect. [ABSTRACT FROM AUTHOR]

Background: Low 25-hydroxy vitamin D (25(OH)D) levels have been associated with an increased risk of albuminuria, however an association with glomerular filtration rate (GFR) is not clear. We explored the relationship between 25(OH)D levels and prevalent chronic kidney disease (CKD), albuminuria and impaired GFR, in a national, population-based cohort of Australian adults (AusDiab Study). Methods: 10,732 adults ≥25 years of age participating in the baseline survey of the AusDiab study (1999-2000) were included. The GFR was estimated using an enzymatic creatinine assay and the CKD-EPI equation, with CKD defined as eGFR <60 ml/min/1.73 m2. Albuminuria was defined as a spot urine albumin to creatinine ratio (ACR) of ≥2.5 mg/mmol for men and ≥3.5 for women. Serum 25(OH)D levels of <50 nmol/L were considered vitamin D deficient. The associations between 25(OH)D level, albuminuria and impaired eGFR were estimated using multivariate regression models. Results: 30.7% of the study population had a 25(OH)D level <50 nmol/L (95% CI 25.6-35.8). 25(OH)D deficiency was significantly associated with an impaired eGFR in the univariate model (OR 1.52, 95% CI 1.07-2.17), but not in the multivariate model (OR 0.95, 95% CI 0.67-1.35). 25(OH)D deficiency was significantly associated with albuminuria in the univariate (OR 2.05, 95% CI 1.58-2.67) and multivariate models (OR 1.54, 95% CI 1.14-2.07). Conclusions: Vitamin D deficiency is common in this population, and 25(OH)D levels of <50 nmol/L were independently associated with albuminuria, but not with impaired eGFR. These associations warrant further exploration in prospective and interventional studies. [ABSTRACT FROM AUTHOR]

Background: Reduction of proteinuria and blood pressure (BP) with blockers of the renin-angiotensin system (RAS) impairs the progression of chronic kidney disease (CKD). The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD. Study Design: Open randomized cross-over trial. Setting and Participants: Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/ 24 hours. Intervention: Eight weeks of once-daily administration of add-on 25-50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade. Outcomes & Measurements: 24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance. Results: The mean urinary albumin excretion was 22% [CI: 14,28], P<0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p-potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia. Limitations: Open label, no wash-out period and a moderate sample size. Conclusions: In non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium. [ABSTRACT FROM AUTHOR]

Purpose Activation of the rennineangiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria. Study design Thirty-two patients with non-nephroticrange proteinuria (0.045-0.23 g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50 mg/day, and the doses were titrated up to 100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24 months. Results Baseline characteristics in the two groups were similar. After 24 months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03 g/mmol, p<0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group. Conclusion Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD. [ABSTRACT FROM AUTHOR]

Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic-normoproteic diet (Phase I) and the effect of normosodic-normoproteic diet plus enalapril (0.18-0.27 mg/kg/day) or losartan (0.89-1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1-49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23-45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ= 8.9, p = 0.015). These results suggest that: (1) a normosodic-normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated. [ABSTRACT FROM AUTHOR]

The balance between angiotensin II (ANG II) and nitric oxide plays an important role in renal function and is thought to contribute to the progression of renal injury in experimental hypertension. In the present study, we investigated the extent of blood pressure (BP)-dependent and BP-independent pathways of renal injury following 2 wk of hypertension produced by intravenous infusion of ANG II (5 ng∙kg-1∙min-1)+Nω-nitro-l-arginine methyl ester (l-NAME; 1.4 μg∙kg-1∙min-11) in male Sprague-Dawley rats. An aortic balloon occluder was positioned between the renal arteries to maintain (24 h/day) BP to the left kidney (servo-controlled) at baseline levels, whereas the right kidney (uncontrolled) was chronically exposed to elevated BP. Over the 14-day experimental protocol, the average BP to uncontrolled kidneys (152.7 ± 1.8 mmHg) was significantly elevated compared with servo-controlled (113.0 ± 0.2 mmHg) kidneys and kidneys from sham rats (108.3 ± 0.1 mmHg). ANG II+l-NAME infusion led to renal injury that was focal in nature and mainly confined to the outer medulla. Despite the differences in BP between servo-controlled and uncontrolled kidneys, there was a similar ~3.5-fold increase in renal outer medullary tubular injury, ~2-fold increase in outer medullary interstitial fibrosis, ~2-fold increase in outer medullary macrophage infiltration, and a significant increase in renal oxidative stress, all of which are indicative of BP-independent mediated pathways. The results of this study have important implications regarding the pathogenesis of renal injury in various experimental models of hypertension and provide novel insights regarding the variable association observed between hypertension and renal injury in some human populations. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Inhibition of the renin–angiotensin–aldosterone system (RAAS) has shown to slow chronic kidney disease (CKD) progression. This is most notable at the earlier stages of diabetic and proteinuric nephropathies.Objective. Here, we observed the impact of discontinuation of angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptors blockers (ARB) in patients with advanced kidney disease.Methods. 52 patients (21 females and 31 males) with advanced CKD (stages 4 and 5), who attended our low clearance clinic (LCC) in preparation for renal replacement therapy (RRT). Mean age was 73.3 ± 1.8 years with an estimated glomerular filtration rate (eGFR) of 16.38 ± 1 ml/min/1.73 m2. Baseline urine protein:creatinine ratio (PCR) was 77 ± 20 mg/mmol. 46% suffered from diabetes mellitus. Patients were followed for at least 12 months before and after ACEi/ARB were stopped.Results. 12 months after discontinuation of ACEi/ARB eGFR increased significantly to 26.6 ± 2.2 ml/min/ 1.73 m2 (p = 0.0001). 61.5% of patients had more than a 25% increase in eGFR, whilst 36.5% had an increase exceeding 50%. There was a significant decline in the eGFR slope −0.39 ± 0.07 in the 12 months preceding discontinuation. The negative slope was reversed +0.48 ± 0.1 (p = 0.0001). Mean arterial blood pressure (MAP) increased from 90 ± 1.8 mmHg to 94 ± 1.3 mmHg (p = 0.02), however ≥50% of patients remained within target. Overall proteinuria was not affected (PCR before = 77 ± 20 and after = 121.6 ± 33.6 mg/mmol).Conclusion. Discontinuation of ACEi/ARB has undoubtedly delayed the onset of RRT in the majority of those studied. This observation may justify a rethink of our approach to the inhibition of the RAAS in patients with advanced CKD who are nearing the start of RRT. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Proteinuric diabetic patients with reduced glomerular filtration rate (GFR) are at high risk of renal and cardiovascular disease progression and treatment-related adverse events. This post hoc analysis assessed the efficacy and safety of aliskiren added to the maximal recommended dose of losartan according to baseline estimated GFR (eGFR) (stage 1-3 chronic kidney disease [CKD]). RESEARCH DESIGN AND METHODS -- In the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study, 599 hypertensive patients with type 2 diabetes and nephropathy received 6 months of aliskiren (150 mg daily titrated to 300 mg daily after 3 months) or placebo added to 100 mg losartan and optimal antihypertensive therapy. Exclusion criteria included eGFR <30 ml/min per 1.73 m² and serum potassium >5.1 mmol/l. RESULTS -- Baseline characteristics were similar between treatment groups in all CKD stages. The antiproteinuric effects of aliskiren were consistent across CKD stages (19, 22, and 18% reduction). In the stage 3 CKD group, baseline serum creatinine levels were equal, but renal dysfunction, prespecified as a postrandomization serum creatinine elevation >176.8 µmol/l (2.0 mg/dl) occurred more frequently in the placebo group (29.2 vs. 13.6%, P = 0.032). Serum potassium elevations >5.5 mmol/l (based on a single measurement) were more frequent with aliskiren (22.5 vs. 13.6%) in stage 3 CKD. Adverse event rates were similar between treatments, irrespective of CKD stage. CONCLUSIONS -- Aliskiren added to losartan reduced albuminuria and renal dysfunction and was well tolerated, except for hyperkalemia (stage 3), independent of baseline CKD stage in patients with type 2 diabetes, hypertension, and nephropathy. [ABSTRACT FROM AUTHOR]

Inhibitors of the renin-angiotensin system (RAS) form a cornerstone in the treatment of kidney disease. These drugs lower blood pressure and albuminuria, and afford renal protection. Dual therapy with an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker have been shown to be more effective in reducing blood pressure and albuminuria than the single use of these agents. It was therefore expected that the combination of these drugs could delay the progression of renal disease. However, the ONTARGET renal analysis suggests that the use dual-agent RAS leads to increased renal risk. This led to vivacious discussions about the benefits and risks of dual-agent RAS in patients with nephropathy. We will review the ONTARGET trial design and interpretation, and offer implications for novel trials. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

By most estimates, we have an increasing worldwide end-stage renal disease (ESRD) epidemic. This is despite at least two decades of intensified reno-protection strategies, including attempts at optimal hypertension management, optimization of diabetic control, smoking cessation efforts, and the extensive application of renin–angiotensin–aldosterone system (RAAS) blockade in both diabetic and nondiabetic chronic nephropathies. The current consensus is that chronic kidney disease (CKD) progression to ESRD is a continuous, progressive, and predictable loss of estimated glomerular filtration rate (eGFR) in CKD patients, inexorably leading to ESRD. Our recent experience in a Mayo Health System Hypertension Clinic, as well as new reports associating ESRD development in CKD patients with episodes of acute kidney injury (AKI), led us to hypothesize that CKD to ESRD progression may not be that predictable, after all. Among a 100 high-risk CKD patient cohort that we have followed up prospectively since 2002, we demonstrated that in 15 of 17 (88%) patients who progressed to ESRD, progression from CKD to ESRD was unpredictable, nonlinear, abrupt, and rapid, and this followed AKI secondary to medical and surgical events. We have coined a new term, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD), to represent this unrecognized syndrome. Larger studies are warranted to confirm our single-center findings. If confirmed to represent a significant proportion of the ESRD population, at least here in the United States, this finding will demand major paradigm shifts in the current concepts of reno-protection and “A-V Fistula first” programs. [ABSTRACT FROM AUTHOR]

Background. In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function. [ABSTRACT FROM PUBLISHER]

Sub-Saharan Africa is the epicentre of the HIV pandemic but there are few reports of HIV-related kidney diseases in children in this region. This study aimed to determine the prevalence of proteinuria in HIV-infected children at the Lagos University Teaching Hospital. Proteinuria was determined using urine protein–creatinine ratio. CD4+ cell count was determined for all the HIV-infected children. The mean age of the HIV-infected children was 74.4 ± 35.6 months with a male: female ratio of 3:2. Compared with 6% of the 50 controls 20.5% of the 88 HIV-infected children had proteinuria (p = 0.026). Of 20 children with advanced clinical stage 40% had proteinuria compared with 14.7% of 68 children with milder stage (p = 0.004). Similarly, proteinuria was commoner among those with severe immunosuppression (p = 0.014). HAART use was not associated with significant difference in proteinuria prevalence (p = 0.491). Proteinuria was frequent among HIV-infected children, especially among those with advanced disease. [ABSTRACT FROM PUBLISHER]

The existence of the renin–angiotensin–aldosterone system was first postulated over 100 years ago. Following the identification of all the major components, came the discovery of their potential pathogenicity in cardiovascular and renal disease. The introduction of drugs that inhibit the synthesis or actions of this system has prompted a number of trials that have largely shaped how cardiovascular and renal disease is managed today. The continued discovery of yet more components of this system promises to further our understanding of its influence on disease processes and herald the development of more highly selective drugs, ensuring that the renin–angiotensin–aldosterone system will continue to be a key area of interest for many years to come. [ABSTRACT FROM AUTHOR]

Background/Aim: A high percentage of patients with chronic kidney disease has nonprogressive disease. Classification with respect to rate of change in glomerular filtration rate (GFR) would permit a more targeted approach to these patients. The aim of this study was to study predictors of rate of change in GFR in a population-based cohort. Methods: All prevalent patients with chronic kidney disease stage 3 in a well-defined population in Northern Europe between 1994 and 2003 were included. Clinical and biochemical data were collected from primary care and hospital medical records. GFR was estimated from creatinine with the recalibrated Modification of Diet in Renal Disease Study equation. Rate of change in GFR were explored in two-level multivariate linear regression models. Results: A total of 1,224 patients were included. The mean age (76.5 years) was higher and mean rate of decline in GFR slower (1.5 ml/min/1.73 m2/year) than in studies of selected patient groups. A total of 60% of the patients suffered from comorbid conditions, 90% had hypertension. Male gender, diabetes, proteinuria and higher mean arterial pressure were independent predictors of a faster decline in GFR. Conclusion: The similarity of the identified predictors with those found in clinical trials of more selected patients may indicate the potential for improved treatment of older chronic kidney disease patients with multiple comorbidities by better adherence to existing guidelines. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cantarovich F, Martinez F, Heguilen R, Thervet E, Mamzer Bruneel M-F, Gonzalez C, Legendre C. Proteinuria >0.5 g/d, a prevalent prognostic factor for patient and graft survival in kidney transplantation. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01043.x © 2009 John Wiley & Sons A/S. Proteinuria >0.5 g/d (HP) and serum creatinine (Scr) >120 μmol/L (HSC) at three months, two and five yr were compared as prognostic factors in kidney transplantation. We retrospectively analyzed 454 first transplants (follow-up: 100 ± 3.2 months). Donor/recipient age, sex, panel reactive antibody (PRA), HLA mismatches, cold ischemia time, delayed graft function, acute rejection, blood pressure and its treatment, diabetes and anti-calcineurin use were also evaluated. Cox proportional hazard regression with time-dependent covariates to control for potentially confounding factors was used to analyze survival. The Kaplan–Meier product–limit estimate for survival according to urine protein excretion (≤ or >0.5 g/d) or Scr (≤ or >120 μmol/L) along with the log-rank test for all comparisons were computed. Statistical significance was set with p-value < 0.05. Results: HSC is a prognostic factor of graft survival (HR: 2.54; 95% CI: 1.98–3.10; p < 0.01) only at five yr, but it does not predict mortality at any period. HP at three months (HR: 2.07; 95% CI: 1.70–2.43; p < 0.001) and at two yr 3.03 (2.54–3.51; p < 0.001) significantly predicts graft failure. HP at two yr is the prevailingly prognostic factor of patient survival in kidney transplantation (HR: 3.30; 95% CI: 1.94–5.62; p < 0.0001). [ABSTRACT FROM AUTHOR]

Objective. Autosomal dominant polycystic kidney disease (ADPKD) is progressive, resulting in end-stage kidney failure in most patients. Experimental and clinical studies have suggested that statins may slow the progression of chronic kidney disease in general and ADPKD specifically. Material and methods. This randomized open-label clinical trial was conducted to assess the effect of pravastatin 20 mg on kidney function and urinary protein excretion in patients with ADPKD. Sixty patients were initially recruited but 49 of these received either pravastatin 20 mg or no treatment for 2 years. Trial visits were conducted every 3 months, assessing kidney function by estimated glomerular filtration rate and 24 h urine creatinine clearance and urinary protein excretion. Results. There were no significant ( p > 0.05) changes in markers of kidney function or urinary protein excretion between groups over the 2 years despite a significant fall in total serum cholesterol in pravastatin-treated patients ( p = 0.029). Conclusion. This trial found that taking 20 mg pravastatin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD. The lack of statistical power limits the external validity of these findings. A larger, longer duration study using a higher dose of a more potent statin is required. [ABSTRACT FROM AUTHOR]

Chronic kidney diseases share common pathogenic mechanisms that, independently from the initial injury, lead to glomerular hyperfiltration, proteinuria, and progressive renal scarring and function loss. Inhibition of the renin angiotensin system (RAS) has been consistently found to reduce or halt the progressive deterioration of renal function through reduction of blood pressure and proteinuria, the two main determinants of renal function decline. In few instances, RAS inhibition may even promote amelioration of the glomerular filtration rate. Animal data suggest that chronic therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor type I blockers promotes regression of glomerulosclerosis, even in later phases of the disease. In humans, studies investigating the effect of angiotensin II inhibition on renal structural changes have shown inconsistent results, possibly due to small numbers and/or short duration of follow-up. Whether regression of glomerulosclerosis relies on a direct regenerative effect of RAS inhibition or on spontaneous kidney self-repair after the injury has been removed is still unknown. Improved understanding of mechanisms that promote renal regeneration may help in designing specific therapies to prevent the development of end-stage renal disease. This is a desirable goal, considering the economic burden of chronic kidney diseases and their effect on morbidity and mortality. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II), the central product of renin-angiotensin system, has a role in the etiology of hypertension and in pathophysiology of cardiac and renal diseases in humans. Other functions of Ang II include effects on immune response, inflammation, cell growth and proliferation, which are largely mediated by Ang II type 1 receptor (AT1). Several experimental studies have demonstrated that Ang II acts through AT1 as a mediator of normal aging processes by increasing oxidant damage to mitochondria and in consequences by affecting mitochondrial function. Recently, our group has demonstrated that the inhibition of Ang II activity by targeted disruption of the Agtr1a gene encoding Ang II type 1A receptor (AT1A) in mice translates into marked prolongation of life span. The absence of AT1A protected multiple organs from oxidative damage and the alleviation of aging-like phenotype was associated with increased number of mitochondria and upregulation of the prosurvival gene sirtuin 3. AT1 receptor antagonists have been proven safe and well-tolerated for chronic use and are used as a key component of the modern therapy for hypertension and cardiac failure, therefore Ang II/AT1 pathway represents a feasible therapeutic strategy to prolong life span in humans. [ABSTRACT FROM AUTHOR]

The article offers information on the evidence-based guidelines for the better management and treatment of chronic kidney disease (CKD). As stated, the diagnosis of CKD is confirmed by the analysis of Glomerular filtration rate (GFR) or abnormal laboratory findings. It further suggests screening of diabetic patients for kidney diseases with the help of tests measuring the presence of albumin and creatinine in urine, spot-urine sample, serum creatinine and eGFR.

Much focus has been placed on the role of the renin–angiotensin system as a mediator of the progression of chronic kidney disease. Novel therapeutic strategies to inhibit the negative impact of renin–angiotensin activation, including dual therapy with an angiotensin-converting enzyme inhibitor and an angiotensin-receptor blocker, have been suggested to achieve more complete disruption of the renin–angiotensin system. The role played by aldosterone, a target of angiotensin II, in the progression of chronic kidney disease has become a subject of significant interest over the past decade. Experimental studies in animals have shown that persistently elevated aldosterone levels lead to pathohistological changes in the kidney, along with renal and cardiac fibrosis. Incomplete suppression of aldosterone may, therefore, contribute to the deleterious effects of the renin–angiotensin system in the setting of chronic kidney disease. Clinical trials in adults have shown a potential role for mineralocorticoid receptor blockers to delay further the development of end-stage renal disease by completing renin–angiotensin blockade. In adults, mineralocorticoid receptor blockade produces a significant anti-proteinuric effect and has minimal risk of causing hyperkalemia if the condition of the patients is closely monitored. Further studies will need to be conducted to determine whether mineralocorticoid receptor blockers are equally effective and safe for the treatment of chronic kidney disease in children. [ABSTRACT FROM AUTHOR]

Background. Immunoglobulin A nephropathy (IgAN) is the most common cause of chronic renal failure among primary glomerulonephritis patients. The best treatment for IgAN remains poorly defined. We planned a long-term, prospective, open-label, multicentre, centrally randomized controlled trial to assess whether the combination of prednisone and ramipril was more effective than ramipril alone in patients with proteinuric IgAN. [ABSTRACT FROM PUBLISHER]

Background. Higher levels of urinary albumin excretion predict future hypertension and chronic kidney disease. Post-menopausal hormone use may influence the renin–angiotensin system and renal endothelial function, impacting albumin excretion. The association between post-menopausal hormone use and albuminuria is not well defined. [ABSTRACT FROM PUBLISHER]

Whether the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker inhibitor (ACEI/ARB) is beneficial in renal transplant recipients remains controversial. In this retrospective study on 505 renal transplant recipients, we analyzed blood pressure and graft survival according to antihypertensive treatment with ACE-I/ARB and/or calcium channel blockers (CCB) over a period of 10 years. Patients were stratified according to their blood pressure 1 year after transplantation [controlled (≤130/80 mmHg; CTR, 181 patients) and noncontrolled (>130/80 mmHg; non-CTR, 324 patients)] and according to antihypertensive treatment (ACE-I/ARB and/or CCB taken for at least 2 years). One year after transplantation, 88.4% of CTR and 96.6% of non-CTR received antihypertensive treatment ( P < 0.05). Graft survival was longer in CTR than in non-CTR ( P < 0.05). Importantly, graft survival was longer in patients who received long-term treatment with ACEI/ARB, CCB, or a combination of ACEI/ARB and CCB ( P < 0.001). The beneficial effect of ACEI/ARB therapy was more pronounced in non-CTR compared with that of CTR. We conclude that blood pressure control is a key target for long-term graft survival in renal transplant patients. Long-term ACEI/ARB and CCB therapy is beneficial for graft survival, especially in patients with diabetes and/or albuminuria. [ABSTRACT FROM AUTHOR]

Background: Random urine protein-to-creatinine (PCR) and albumin-to-creatinine (ACR) ratios have been proposed as alternatives to 24 h urine measurements to simplify sample collection and overcome errors. The aim of this study was to examine the ability of PCR and ACR to predict urinary 24 h protein and albumin loss, respectively, in patients with kidney disease, and determine the most appropriate time of collection. Methods: Eighty-three patients were recruited from a renal outpatient clinic. In a 24 h period, each collected an early-morning urine (EMU), second and third voids, and the remaining urine passed that day. PCR and ACR were determined in random urines and compared with the 24 h loss of protein and albumin, respectively. Results: For all patients, median (range) 24 h urine protein and albumin losses were 220 (30-15600) and 60 (<8-10,557) mg, respectively. Ratios derived from each of three random urines correlated well with 24 h protein or albumin loss (Spearman's rs > 0.87, P < 0.0001). Receiver operator characteristic (ROC) curve analysis showed PCR accurately predicted both an abnormal 24 h urine protein ≥150 mg/24 h (areas under curves [AUC] 0.90-0.92) and significant proteinuria above 300 mg/ 24 h (AUC between 0.97 and 1.00). ACR accurately predicted both an abnormal 24 h urine albumin ≥ 30 mg/24 h (AUC 0.98 to 0.99) and frank albuminuria at ≥ 300 mg/24 h or ≥ 700 mg/24 h (AUC between 0.99 and 1.00). EMU and random urines performed equally well in predicting proteinuria and albuminuria from PCR and ACR, respectively. Conclusions: By careful choice of cut-offs, both PCR and ACR can be used in patients with kidney disease to rule in or rule out abnormal 24 h losses of protein and albumin. EMU and, importantly, random samples can be used as surrogates for 24 h urine collections. [ABSTRACT FROM AUTHOR]

The primary purpose of guidelines should be to improve patient care by providing an avenue for healthcare professionals to participate in the assessment of appropriate care, based on sound medical reasoning and robust scientific knowledge. Guidelines are usually meant to be evidence-based when they are derived from systemic reviews of the relevant literature. Nephrology as a medical subspeciality lags behind other clinical disciplines when it comes to availability of high-quality clinical studies with hard clinical outcomes. In the absence of robust clinical evidence, recommendations in renal guidelines are overwhelmingly opinion-based and reflect the experience of the various experts. Unfortunately, no guidelines are detailed enough to provide recommendations for individual patients with different types and severity of co-morbidities. We propose that guidelines should be viewed as desirables and should not replace a common sense clinical approach to patient care by an autonomously practicing competent clinician. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The majority of complement factor H mutations associated with atypical hemolytic uremic syndrome (HUS) are heterozygous. Homozygous mutations causing atypical hemolytic uremic syndrome are rare. We report a 7-month-old boy with HUS, severe hypocomplementemia (low C3 and normal C4 levels), and extremely low circulating levels of factor H. Genetic analysis showed homozygous 4 bp deletion in the gene encoding factor H in the patient, with his parents being carriers. The patient showed progression to end-stage renal disease and is presently on chronic ambulatory peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for more than half of all renal failure in children. For young adults with CAKUT two questions are paramount: what is the prognosis and what is the best management to improve outcome? The paediatric literature shows that prognostic factors are glomerular filtration rate (GFR) and the presence of proteinuria. We reviewed data from 101 young adult patients with either primary vesico-ureteric reflux and renal dysplasia or obstructive uropathy. Patients had an estimated GFR (eGFR) of ≤60 ml/min per 1.73 m2 body surface area and had had at least 5 years of follow up (median 162 months). There was a strong correlation between the amount of proteinuria at the start and overall rate of decline. Angiotensin-converting enzyme inhibitors (ACEIs) slowed declining renal function at all levels of function, but this only had a significant effect on renal outcome when eGFR was >35 ml/min. The ACEI benefit increased with time. Rate of decline was slower than reported for other diseases and was only −2.4 ml/min per year for those reaching the start of dialysis. Outcome is predictable by the level of residual renal function (GFR). Nevertheless, function remains stable while proteinuria is minimal. Short-term studies overestimate rates of deterioration. [ABSTRACT FROM AUTHOR]

The article discusses the study which explores the risk of hyperkalemia for nondiabetic patients with chronic kidney disease (CKD) and administered with antihypertensive therapy. In the study, researchers used the African American Study of Kidney Disease and Hypertension (AASK) database to determine CKD treated with angiotensin converting enzyme inhibitors with dihydropyridine calcium. It shows that nondiabetic patients with hypertensive CKD including diuretic for the risk of hyperkalemia.

Limited pediatric data on allograft survival from advanced aged kidney donors exist. To determine the influence of donor source and age on allograft survival in pediatric renal transplant recipients, we analyzed the OPTN database. Allograft survival for 7291 pediatric renal transplants was evaluated. Up to five yr post-transplantation, graft survival was higher for LD vs. DD recipients. At seven yr, allograft survival was 71% in 18–54 yr-old LD recipients, 59.1% in ≥55 yr-old LD, and 45.1% in ≥50 yr-old DD recipients. An approximate 35% improvement in allograft survival in 18–54 yr-old LD recipients was observed. Multivariate results showed that recipients of LD 35–49 (aRR 0.66, 95% CI 0.55–0.80) and LD 50–54 (aRR 0.65, 95% CI 0.45–0.94) have a graft survival advantage over the ideal DD. In LD ≥55 yr, no improvement in graft survival was observed when compared with the 18–34 yr-old DD. In summary, we observed in a pediatric population, <55 yr-old LD kidneys afford improved long-term allograft survival when compared with DD kidney recipients. Increasing awareness of the long-term graft survival advantage for children receiving an LD kidney, even from older donors, should be a priority. [ABSTRACT FROM AUTHOR]

Aims: To investigate risk factors for progression to microalbuminuria in normoalbuminuric hypertensive patients. Methods: In a longitudinal study, 173 previously treated normoalbuminuric hypertensive patients with high cardiovascular risk (70% diabetics) were evaluated at study entry and after 12 months. Levels of urinary albumin excretion (UAE; study entry and end of study) were compared between patients remaining normoalbuminuric (RNA) and progressors to non-normoalbuminuric (NNA) levels. Results: Out of 173 patients (59 ± 13 years), 12% evolved to NNA levels. At baseline, NNA and RNA groups did not differ in age, sex, diabetes, lipids, blood pressure (BP), drug therapy, or glomerular filtration rate. In comparison with RNA patients, the NNA group showed higher hypertension duration, greater UAE and percentage of patients with UAE ≥10 mg/g creatinine (76.2 vs. 45.4%) at study entry and higher BP levels (158/92 ± 25/10 vs. 143/83 ± 20/12 mm Hg) at study end (all p < 0.05). Logistic regression analysis identified absolute UAE values at study entry and study end variation of BP and cholesterol as independent contributors to the increase in the log odds of developing microalbuminuria. Conclusions: Normoalbuminuric hypertensives with UAE within the upper two thirds of normal range are 3 times as likely to develop microalbuminuria after 1 year. A poor BP and lipid control are also associated with increased risk of microalbuminuria. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A fundamental clinical problem in treating patients with chronic kidney disease (CKD) is designing their diets: an excess of protein leads to the accumulation of uremic toxins, whereas a diet insufficient in protein could lead to loss of lean body mass. The benefits of dietary protein restriction include reducing the accumulation of metabolic waste products that can suppress appetite and stimulate muscle protein wasting. There also is a potential for slowing the loss of kidney function. Unfortunately, advanced CKD is strongly associated with a protein wasting syndrome that is directly correlated with morbidity and mortality. Fortunately, the mechanisms underlying negative responses to an excess of dietary protein, including the causes of the wasting syndrome, are beginning to be understood. We have examined how dietary protein influences the mechanisms causing protein wasting, and we propose a framework for approaching the variable dietary protein requirements in patients with CKD or end-stage kidney disease. [ABSTRACT FROM AUTHOR]

Background. A continuous increase in number of CKD patients entering ESRD is a growing public health threat, which reflects the present therapeutic failure usually initiating at the late stage of CKD. Objective. To study the mechanism of vascular repair in CKD patients associated with mildly impaired renal function, which included angiogenic factors such as VEFG, angiopoietin-1, and flt-1 (VEGFR1); and antiangiogenic factors such as angiopoietin-2 and KDR (VEGFR2). Results. A mild defect in angiogenic factor—namely, angiopoietin-1—was observed, whereas VEGF and flt-1 (VEGFR1) were within normal limit. Also, antiangiogenic factor—namely, angiopoietin-2—was mildly elevated, whereas KDR (VEGFR2) remained within normal limit. Conclusion. The mechanism of vascular repair appears to be adequately functional in the early stage of CKD. Therapeutic intervention at this stage can improve renal perfusion and restore renal function as indicated in normoalbuminuric, type 2 diabetic nephropathy. The authors encourage changing the conceptual view of treatment under common treatment at late stage of CKD to treatment at early stage of CKD under an environment favorable for renal regeneration. [ABSTRACT FROM AUTHOR]

Some calcium channel blockers (CCBs) have renoprotective effects. Our aim was to compare the effects of different subclasses of CCBs on the deterioration of renal function in chronic kidney disease (CKD). This is a prospective, observational cohort study in a single center. The subjects were 107 nondiabetic CKD patients. The rate of deterioration of estimated glomerular filtration rate (ΔeGFR) was calculated by [last visit eGFR — baseline eGFR/follow-up duration]. Multivariate analysis was performed using the change in urinary protein (ΔUP) and ΔeGFR during follow-up as response variables. CCB subclasses were L-type in 76 patients, T- and L-type in 28 patients, and nondihydropyridines in 6 patients. Multiregression analysis indicated that higher baseline proteinuria (UP) and the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers were associated with the decrease of UP, while the use of L-type CCBs, prednisolone, and probucol was associated with the increase of UP. The use of T- and L-type CCBs, ACEIs and diuretics was associated with a good outcome in terms of ΔeGFR, whereas chronic glomerulonephritis, polycystic kidney disease, and higher baseline eGFR and UP were associated with a poor outcome. It is suggested that the use of T- and L-type CCB among other subclasses may improve the outcome of patients with nondiabetic CKD in terms of renal function. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a common and costly medical condition, and currently available therapeutic options remain unsatisfactory. Vitamin D analogues are widely used for the bone and mineral disorder associated with CKD. However, accumulating evidence suggests that vitamin D analogues may have actions other than their effects on bone and mineral metabolism. In this article, we review the following aspects on the use of vitamin D analogues for the treatment of CKD: (1) epidemiological studies showing that patients with late-stage CKD have better survival than untreated patients; (2) animal studies showing that vitamin D analogues may retard the progression of CKD; (3) human studies on the anti-proteinuric and possibly renal protecting effects of vitamin D analogues in CKD and (4) the potential mechanisms of its therapeutic benefit. Nonetheless, definitive proof of the clinical benefits by randomized control trial would be necessary before one could advocate the routine use of vitamin D analogues for the treatment of CKD patients. [ABSTRACT FROM PUBLISHER]

Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk factor for progression of the disease, indicating the need for an effective and safe treatment even in such cases. Studies carried out to date have indicated that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein excretion and preserve renal function in adult IgA-N. However, no prospective study of ACEI only for childhood IgA-N has yet been carried out. In this prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria [morning urinary protein/creatinine ratio (uP/Cr) ≥ 0.2 g/g]. Thirty-three patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan–Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18 g/m2/day ( p < 0.0001). Of the 40 patients treated, five (12.5%) showed dizziness, and four of these five needed the lisinopril dose reduced. However, lisinopril therapy was continued in all patients during the 2-year treatment period. No other side effect, such as cough, was observed. We conclude that the efficacy and safety of lisinopril is seemingly acceptable for the treatment of children with mild IgA-N. [ABSTRACT FROM AUTHOR]

ICGN/Oa mice are used to study the pathophysiological mechanisms underlying proteinuria-induced chronic kidney disease (CKD). Recently, a mutation of tensin2 gene (Tns2) was suggested to be responsible for proteinuria in the inbred ICGN mice. We identified the wild-type (+/+), heterozygous (+/nep), and homozygous (nep/nep) ICGN/Oa mice by PCR assay. The homozygotes developed proteinuria, resulting in nephrotic syndrome (NS) as early as 5 weeks and CKD by 15 weeks. However, the heterozygotes did not show the symptoms of these renal failures. These results indicate that the homozygous tensin2 mutation is necessary for the ICGN/Oa mice to develop proteinuria-induced CKD. Furthermore, we examined the time course of tubulointerstitial fibrosis and the kinetics of tubular epithelial cells (TECs) in the ICGN/Oa mice using immunohistochemical and TUNEL assays. In the renal parenchyma of the five-week-old homozygotes, the expression of α-SMA and type I collagen were higher than those in the age-matched wild-type. Additionally, increased TEC proliferation was found at 5 weeks, and increased TEC apoptosis was by 15 weeks in the homozygotes. Tubulointerstitial fibrosis precedes TEC apoptosis in the proteinuria-induced CKD model mice, and that tubulointerstitial fibrosis may be the triggering event of the disease. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is generally regarded as a final common pathway of several renal diseases, often leading to end-stage kidney disease (ESKD) and a need for renal replacement therapy. Estimated GFR (eGFR) has been used to predict this outcome recognizing its robust association with renal disease progression and the eventual need for dialysis in large, mainly cross-sectional epidemiological studies. However, GFR is implicitly limited as follows: (1) GFR reflects only one of the many physiological functions of the kidney; (2) it is dependent on several non-renal factors; (3) it has intrinsic variability that is a function of dietary intake, fluid and cardiovascular status, and blood pressure especially with impaired autoregulation or medication use; (4) it has been shown to change with age with a unique non-linear pattern; and (5) eGFR may not correlate with GFR in certain conditions and disease states. Yet, many clinicians, especially our non-nephrologist colleagues, tend to regard eGFR obtained from a simple laboratory test as both a valid reflection of renal function and a reliable diagnostic tool in establishing the diagnosis of CKD. What is the validity of these beliefs? This review will critically reassess the limitations of such single-focused attention, with a particular focus on inter-individual variability. What does science actually tell us about the usefulness of eGFR in diagnosing CKD? [ABSTRACT FROM AUTHOR]

AbstractThe term ‘cardiorenal syndrome’ (CRS) has increasingly been used in recent years without a constant meaning and a well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of the heart-kidney interactions, the classification of the CRS today includes 5 subtypes whose etymology reflects the primary and secondary pathology, the time frame and simultaneous cardiac and renal codysfunction secondary to systemic disease. The CRS can generally be defined as a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Type I CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type II CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type III CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type IV CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events. Type V CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. Biomarkers can help to characterize the subtypes of the CRS and to indicate treatment initiation and effectiveness. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help to understand clinical derangements, to make the rationale for management strategies and to design future clinical trials with accurate selection and stratification of the studied population.Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses guidelines for chronic kidney disease management that were developed by the Canadian Society of Nephrology. The guidelines explains key aspects of the management of the disease to promote shared care for these patients by general practitioners and specialists. In particular, these guidelines are for the care of patients who are not undergoing dialysis. The authors offer recommendations from the guidelines on aspects of management of chronic kidney disease. These include strategies for treatment, targets for different abnormalities and frequency of follow-up based on the evidence available.

Activation of filtered complement products on the brush border of the tubular epithelium is thought to be a key factor underlying proteinuria-induced tubulointerstitial injury. However, the mechanism of tubular complement activation is still unclear. Recent studies on mechanisms of complement activation indicate a key role for properdin in the initiation of an alternative pathway. We hypothesized that properdin serves as a focal point for complement activation on the tubulus. We observed a strong staining for properdin on the luminal surface of the tubules in kidney biopsies from patients with proteinuric renal disease. In vitro experiments revealed dose-dependent binding of properdin to proximal tubular epithelial cells (PTEC), whereas no significant binding to endothelial cells was detected. Exposure of PTEC with normal human serum as a source of complement resulted in complement activation with deposition of C3 and generation of C5b-9. These effects were virtually absent with properdin-deficient serum. Preincubation of PTEC with properdin before addition of properdin-depleted serum fully restored complement activation on the cells, strongly suggesting a key role for properdin in the activation of complement at the tubular surface. In proteinuric renal disease, filtered properdin may bind to PTEC and act as a focal point for alternative pathway activation. We propose that this contribution of properdin is pivotal in tubular complement activation and subsequent damage. Interference with properdin binding to tubular cells may provide an option for the treatment of proteinuric renal disease. [ABSTRACT FROM AUTHOR]

The maximum age of recipients expected to benefit with a kidney transplant has increased in the past three decades. In 1980, patients older than age 50 were not listed for a transplant. In 2004, almost 90% aged 50–60 yr with end-stage renal disease were listed, and some were even older than age 80. We summarize previous articles to illustrate how the notion of “senior” has evolved for kidney transplantation, and using data reported to the Organ Procurement Transplant Network, describe characteristics, treatments and outcomes in recipients older than 50 yr. Fractions of male, white, non-obese, unsensitized recipients and use of expanded criteria donors increased in cohorts with increasing recipient age. The percentage of recipients with hypertension or diabetes decreased, but the percentage with cancer increased. The fraction spared steroids increased with increasing age, but other aspects of immunosuppression were not remarkably different. No differences in early outcomes were notable, and elderly recipients likely did not return to dialysis. However, both graft and patient survival rates decreased with increasing age. Although a small fraction was selected, and survival rates were lower, patients older than 80 yr received kidney transplants. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is generally thought to be a progressive disorder regardless of etiology. Over the past 15 years, investigations into the mechanisms of disease progression and treatment designed to slow or halt disease progression have been conducted, largely in the adult kidney disease population. Intervention trials have demonstrated that lowering blood pressure in hypertensive patients and administration of drugs that block the renin–angiotensin aldosterone system are effective at slowing kidney disease progression, including diabetes, hypertension, and various glomerular diseases. In addition, novel strategies including anemia therapy with erythropoietin-stimulating agents have been conducted to determine whether treatment of this common complication of kidney disease can stabilize kidney function. Whereas substantial success has been achieved in more common forms of adult kidney disease such as diabetes and hypertension, slowing progression of some immune-mediated glomerular disease such as lupus nephritis and immunoglobulin A (IgA) nephropathy remain a great challenge. Moreover, there is no proven strategy, including multifactorial interventions, that clearly halts progressive chronic kidney disease that has been studied prospectively in a large-scale, long-term trial. The purpose of this review is to discuss these trials, as they form the underpinnings for current clinical practice guidelines in adults with chronic kidney disease. [ABSTRACT FROM AUTHOR]