BMC Nephrology - Latest Articles

Age-related associations of hypertension and diabetes mellitus with chronic kidney disease

Tareq Islam — 2009-06-30T00:00:00Z

Background: Studies suggest end-stage renal disease incidence and all-cause mortality rates among patients with chronic kidney disease (CKD) differ by age. The association of diabetes mellitus and hypertension with CKD across the adult lifespan is not well established. Methods: Data from NHANES 1999-2004 were used to determine the association of risk factors for stage 3 or 4 CKD (n=12,518) and albuminuria (n=12,778) by age grouping (20 to 49, 50 to 69, and >=70 years). Stage 3 or 4 CKD was defined as an estimated glomerular filtration rate of 15 to 59 ml/min/1.73m2 and albuminuria as an albumin to creatinine ratio >=30 mg/g.Result: For adults 20 to 49, 50 to 69 and >=70 years of age, the prevalence ratios (95% confidence interval) of stage 3 or 4 CKD associated with hypertension were 1.94 (0.86 - 4.35), 1.51 (1.09 - 2.07), 1.31 (1.15 - 1.49), respectively (p-trend=0.038). The analogous prevalence ratios (95% confidence interval) were 3.01 (1.35 - 6.74), 1.61 (1.15 - 2.25), 1.40 (1.15 - 1.69), respectively, for diagnosed diabetes mellitus (p-trend=0.067); and 2.67 (0.53 - 13.4), 1.35 (0.69 - 2.63), 1.08 (0.78 - 1.51), respectively, for undiagnosed diabetes mellitus (p-trend=0.369). The prevalence ratios of albuminuria associated with hypertension and diagnosed and undiagnosed diabetes mellitus were lower at older age (each p<0.05). Conclusion: Among US adults, diabetes mellitus and hypertension are associated with CKD and albuminuria regardless of age. However, the associations were stronger at younger ages.

Accuracy and limitations of equations for predicting of the glomerular filtration rate during follow-up of patients with non-diabetic nephropathies

Guy Rostoker — 2009-06-25T00:00:00Z

Background: The validity of creatinine-based equations for monitoring renal function in patients with known renal disease is uncertain. Published data are scarce and are mainly restricted to diabetic nephropathy. The aim of this study was to compare the accuracy of creatinine-based prediction equations (original Cockcroft and Gault equation, Cockcroft and Gault equation adjusted for body surface area (BSA), Abbreviated MDRD and Mayo Clinic Quadratic) for the follow-up of patients with non-diabetic nephropathies by comparison with inulin clearance -- the gold standard for GFR estimation. Methods: We analyzed the data from a prospective cohort of 260 European patients with non-diabetic chronic kidney disease (mainly glomerular diseases), 126 of whom had repeated GFR measures by inulin clearance during long-term follow-up. The patients were divided into two subgroups: patients with a deterioration of their renal function during follow-up (n= 65 patients) and those with an improvement (n = 61 patients). We used non parametric ANOVA and Bland and Altman concordance to compare the annual slopes of GFR (ml /min/year) obtained by the prediction equations and the inulin method. Results: In patients whose renal function deteriorated, the original Cockcroft and Gault formula, the BSA-modified Cockcroft and Gault formula, the abbreviated MDRD equation, and the Mayo Clinic Quadratic Equation gave a reliable estimates of the GFR slope, with an acceptable bias. In the subgroup of patients with an improvement in renal function, these creatinine-based formulas underestimated the gain of GFR although this may have less important clinical consequences.

Assessment of arterial stiffness, oxidative stress and inflammation in acute kidney injury

Robert Fassett — 2009-06-18T00:00:00Z

Background: It is well know that arterial stiffness, oxidative stress and inflammation are features of chronic kidney disease. The arterial changes have a multitude of potential interconnected causes including endothelial dysfunction, oxidative stress, inflammation, atherosclerosis and vascular calcification. There is evidence that arterial stiffness becomes progressively worse as CKD progresses. The contribution of the biochemical changes of uremic toxicity to arterial stiffness is less clear. The aim of this study is to elucidate the vascular changes in acute kidney injury. We hypothesise that arterial stiffness will be increased during acute kidney injury and this will return to normal after kidney function recovers.Methods/DesignOne hundred and forty four patients with acute kidney injury defined as an acute increase in serum creatinine to > 133 μmol/l or urea > 14.3 mmol/l or urine output < 410 ml/day will be recruited. Baseline measures of aortic pulse wave velocity, augmentation index, and brachial and central blood pressure will be recorded along with blood measures for oxidative stress and inflammation. Repeat measures will be taken at six and 12 months after the onset of the acute kidney injury.DiscussionThe role and contribution of the biochemical changes to arterial stiffness in the acute phase of kidney disease is not known. This study will primarily assess the time course changes in pulse wave velocity from the onset of acute kidney injury and after recovery. In addition it will assess augmentation index, central blood pressure and oxidative stress and inflammation. This may shed light on the contribution of biochemical kidney toxins on arterial stiffness in both acute kidney injury and chronic kidney disease.Trial RegistrationACTRN 12609000285257

Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients

David Mudge — 2009-06-06T00:00:00Z

Background: Post-transplant anaemia remains a common problem after kidney transplantation, with an incidence ranging from nearly 80% at day 0 to about 25% at 1 year. It has been associated with poor graft outcome, and recently has also been shown to be associated with increased mortality.Our transplant unit routinely administers oral iron supplements to renal transplant recipients but this is frequently accompanied by side effects, mainly gastrointestinal intolerance. Intravenous iron is frequently administered to dialysis patients and we sought to investigate this mode of administration in transplant recipients after noticing less anaemia in several patients who had received intravenous iron just prior to being called in for transplantation. Methods: This study is a single-centre, prospective, open-label, randomised, controlled trial of oral versus intravenous iron supplements in renal transplant recipients and aims to recruit approximately 100 patients over a 12-month period. Patients will be randomised to receive a single dose of 500 mg iron polymaltose (intravenous iron group) or 2 ferrous sulphate slow-release tablets daily (oral iron group). The primary outcome is time to normalisation of haemoglobin post-transplant. Prospective power calculations have indicated that a minimum of 48 patients in each group would have to be followed up for 3 months in order to have a 90% probability of detecting a halving of the time to correction of haemoglobin levels to ≥110 g/l in iron-treated patients, assuming an α of 0.05. All eligible adult patients undergoing renal transplantation at the Princess Alexandra Hospital will be offered participation in the trial. Exclusion criteria will include iron overload (transferrin saturation >50% or ferritin >800 μg/l), or previous intolerance of either oral or intravenous iron supplements.DiscussionIf the trial shows a reduction in the time to correction of anaemia with intravenous iron or less side effects than oral iron, then intravenous iron may become the standard of treatment in this patient group.

A human glomerular SAGE transcriptome database

Jenny Nystrom — 2009-06-05T00:00:00Z

Background: To facilitate in the identification of gene products important in regulating renal glomerular structure and function, we have produced an annotated transcriptome database for normal human glomeruli using the SAGE approach.Description: The database contains 22,907 unique SAGE tag sequences, with a total tag count of 48,905. For each SAGE tag, the ratio of its frequency in glomeruli relative to that in 115 non-glomerular tissues or cells, a measure of transcript enrichment in glomeruli, was calculated. A total of 133 SAGE tags representing well-characterized transcripts were enriched 10-fold or more in glomeruli compared to other tissues. Comparison of data from this study with a previous human glomerular Sau3A-anchored SAGE library reveals that 47 of the highly enriched transcripts are common to both libraries. Among these are the SAGE tags representing many podocyte-predominant transcripts like WT-1, podocin and synaptopodin. Enrichment of podocyte transcript tags SAGE library indicates that other SAGE tags observed at much higher frequencies in this glomerular compared to non-glomerular SAGE libraries are likely to be glomerulus-predominant. A higher level of mRNA expression for 19 transcripts represented by glomerulus-enriched SAGE tags was verified by RT-PCR comparing glomeruli to lung, liver and spleen. Conclusions: The database can be retrieved from, or interrogated online at http://cgap.nci.nih.gov/SAGE. The annotated database is also provided as an additional file with gene identification for 9,022, and matches to the human genome or transcript homologs in other species for 1,433 tags. It should be a useful tool for in silico mining of glomerular gene expression.

Trace elements in end-stage renal disease - unfamiliar territory to be revealed

Adrian Covic — 2009-06-02T00:00:00Z

Although associated with unfavorable outcomes in the general population, abnormal blood levels of various trace elements have not been consistently studied in the end-stage renal disease population (with the notable exception of aluminum). This is surprising, as the uremic patient treated by chronic dialysis loses one major route of trace element excretion and is exposed systematically to a foreign environment (the dialysis fluid) possibly contaminated with significant amounts of potential deleterious trace elements. Moreover, some biological important trace elements may be lost through the dialysis membrane. Most studies to date demonstrated significantly altered blood levels of trace elements in ESRD patients compared to healthy controls. However, the biological impact of these abnormalities in renal disease is largely unknown and should be clarified by future studies. A further step would be the design of well-controlled randomized interventional studies, examining the potential therapeutic benefit of supplementing one or more trace elements in ESRD patients, a population characterized by an impressive mortality due to cardiovascular, infectious and neoplasic disease.

Diagnostic yield of renal biopsies: a retrospective single center review

Bari Scheckner — 2009-05-21T00:00:00Z

Background: Previous studies have examined the spectrum of diseases identified with a kidney biopsy and the complications of the procedure. However, few studies have examined the utility of the test to clarify the diagnosis and guide treatment of pediatric patients. This retrospective, single-center chart review was performed to test the hypothesis that at least 80% of native kidney biopsies provide clinically valuable information that rationally guides diagnosis and patient management. Methods: 200 biopsies performed between January 1, 2000 and June 30, 2008 were reviewed. A scheme composed of six categories was devised to classify the utility of each kidney biopsy. Results: 196 complete case files were available for review. Twenty-four (12.2%) biopsies did not shed light on the diagnosis and were unhelpful in patient management – 21 biopsies (10.7%) were non-diagnostic and 3 (1.5%) failed to yield enough tissue for examination. The number of unhelpful biopsies did not cluster in any specific disease entity. Conclusion: Our findings provide guidance to nephrologists about the total risk of a kidney biopsy, including uninformative results, when seeking informed consent for the procedure. The results suggest an appropriate balance has been reached which maximizes the use of kidney biopsies while minimizing the risk of this invasive procedure (word count: 202).

Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

Wilfried Karmaus — 2009-04-28T00:00:00Z

Background: Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN) is usually considered a non-inflammatory disease. Methods: We examined a marker of inflammation, C-reactive protein (CRP), in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models. Results: Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only), serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function. Conclusion: Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.

Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

Julie Lin — 2009-03-27T00:00:00Z

Background: Increased activation of the renin-angiotensin system (RAS) may be important in promoting coronary heart disease (CHD) and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (AGT1R) and angiotensinogen (AGT) genotypes in type 2 diabetes. Methods: Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). We analyzed single nucleotide polymorphisms (SNPs) associated with cardiovascular pathophysiology (including AGT1R T573C, AGT1R A1166C, and AGT M235T) and presence of renal dysfunction (eGFR<60 ml/min/1.73 m2) or history of CHD. Results: The AGT1R 1166 C-allele was associated with eGFR<60 ml/min/1.73 m2 (multivariable OR 1.63 [1.01, 2.65]) in the HPFS men (n = 733) and in the combined dataset (n = 1566) (OR 1.42 [1.02, 1.98]). The AGT1R 1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]). In NHS women (n = 833), AGT 235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]). Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and AGT1R 1166 C-allele (p = 0.008) and AGT M235T (p = 0.03) in models for CHD. No significant associations were seen between AGT1R T573 C-allele and renal dysfunction or CHD. Conclusion: Polymorphisms in AGT1R and AGT genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between AGT1R 1166 C-allele and AGT 235T and CHD in type 2 diabetes.

Comparison of markers of oxidative stress, inflammation and arterial stiffness between incident hemodialysis and peritoneal dialysis patients - an observational study

Robert Fassett — 2009-03-12T00:00:00Z

Background: Patients on peritoneal and hemodialysis have accelerated atherosclerosis associated with an increase in cardiovascular morbidity and mortality. The atherosclerosis is associated with increased arterial stiffness, endothelial dysfunction and elevated oxidative stress and inflammation. The aims of this study are to investigate the effects of peritoneal and hemodialysis on arterial stiffness, vascular function, myocardial structure and function, oxidative stress and inflammation in incident patients with end stage kidney disease. Methods: This is an observational study. Eighty stage five CKD patients will be enrolled and followed for one-year. Primary outcome measures will be changes in 1) arterial stiffness measured by aortic pulse wave velocity, 2) oxidative stress assessed by plasma F2 isoprostanes and 3) inflammation measured by plasma pentraxin-3. Secondary outcomes will include additional measures of oxidative stress and inflammation, changes in vascular function assessed using the brachial artery reactivity technique, carotid artery intimal medial thickness, augmentation index and trans thoracic echocardiography to assess left ventricular geometry, and systolic and diastolic function. Patients will undergo these measures at baseline (6–8 weeks prior to starting dialysis therapy), then at six and 12 months after starting dialysis.DiscussionThe results of this study may guide the choice of dialysis modality in the first year of treatment. It may also lead to a larger study prospectively assessing the effect of dialysis modality on cardiovascular morbidity and mortality.Trial RegistrationACTRN12609000049279