BMC Nephrology - Latest Articles

End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study

Paul Muntner — 2009-12-02T00:00:00Z

Background: Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized. Methods: The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988. Results: Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p<0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean=103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m2 among ESRD cases and 18.6 kg/m2 and 18.9 kg/m2 among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD. Conclusions: These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.

Quality of life and mortality from a nephrologist's view: a prospective observational study

Seung Seok Han — 2009-11-24T00:00:00Z

Background: Although health-related quality of life (HRQOL) is a potential independent predictor of mortality, nephrologists have shown little interest in HRQOL with respect to mortality in chronic kidney disease (CKD). The aim of this article is to evaluate the impact of HRQOL on mortality in the elderly, who are likely to develop or already have CKD. Methods: Among 1,000 randomly sampled participants aged more than 65 years (sourced from the Korean Longitudinal Study on Health and Ageing), 944 subjects were evaluated for HRQOL. HRQOL was assessed using a 36-item Short-Form health survey (SF36). A cumulative survival rate was calculated according to tertiles of SF36 scores and classified by the presence of CKD (estimated GFR <60 ml/min/1.73 m2). Results: Among 944 subjects, 46.6% had CKD. CKD patients had lower total and physical component scores compared with subjects without CKD. The 3-year cumulative survival rate was 90.0% (non-CKD vs. CKD: 92.6% vs. 87.4%, P = 0.005 by log rank test). After adjusting for multiple variables, a reduced SF36 score (physical and mental components) was a strong predictor of all-cause mortality. Physical components were consistently able to predict mortality after CKD classification, but mental components were statistically significant only in the CKD group. Conclusion: In addition to traditional risk factors of mortality, nephrologists should be aware of HRQOL as a predictor of mortality and should make efforts to improve HRQOL in CKD patients.

Molecular testing for adult type Alport syndrome

Genevieve Pont-Kingdon — 2009-11-17T00:00:00Z

Background: Alport syndrome (AS) is a progressive renal disease with cochlear and ocular involvement. The majority of AS cases are X-linked (XLAS) and due to mutations in the COL4A5 gene. Although the disease may appear early in life and progress to end stage renal disease (ESRD) in young adults, in other families ESRD occurs in middle age. Few of the more than four hundred mutations described in COL4A5 are associated with adult type XLAS, but the families may be very large. Methods: We classified adult type AS mutation by prevalence in the US and we developed a molecular assay using a set of hybridization probes that identify the three most common adult type XLAS mutations; C1564S, L1649R, and R1677Q. Results: The test was validated on samples previously determined to contain one or none of these mutations. In the US, the test's clinical specificity and sensitivity are estimated to be higher than 99% and 75% respectively. Analytical specificity and sensitivity are above 99%. Conclusion: This test may be useful for presymptomatic and carrier testing in families with one of the mutations and in the diagnosis of unexplained hematuria or chronic kidney disease.

Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene

Kyoko Kanda — 2009-11-14T00:00:00Z

Background: Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations.Methods and ResultsWe conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products. Conclusion: mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.

Risk factors for tuberculosis in dialysis patients: a prospective multicenter clinical trial

Antonios Christopoulos — 2009-11-07T00:00:00Z

Background: Profound alterations in immune responses associated with uraemia and exacerbated by dialysis increase the risk of developing active tuberculosis (TB) in chronic haemodialysis patients (HDPs). In the current study, was determined the impact of various risk factors on TB development. Our aim was to identify which HDPs need anti-TB preventive therapy. Methods: Prospective study of 272 HDPs admitted, through a 36-month period, to our institutions. Specific Relative Risk (RR) for TB was estimated, considering age matched subjects from the general population as reference group. Entering the study all patients were tested with tuberculin (TST). Using Cox's proportional hazard model the independent effect of various risk factors associated with TB development was estimated. Results: History of TB, dialysis efficiency, use of Vitamin D supplements, serum albumin and zinc levels were not proved to influence significantly the risk for TB, in contrast to: advanced age (>65 years), BMI, diabetes mellitus, tuberculin reactivity, healed TB lesions on chest X-ray and time on dialysis. Elderly (>70 years old) HDPs (Adjusted RR 25.3, 95%CI 20.4-28.4, P < 0.02), diabetics (Adj.RR 25.3, 95%CI 17.2-21.1, P < 0.03), underweighted (Adj.RR 72.3, 95%CI 65.2-79.8 P < 0.001), tuberculin responders (Adj.RR 41.4, 95%CI 37.9-44.8, P < 0.03), HDPs with fibrotic lesions on chest x-ray (Adj.RR 82.3, 95%CI 51.3-95.5, P < 0.03) and those treated with haemodialysis for < 12 months (Adj.RR 110.0, 95%CI 97.4-135.3, P < 0.001), presented significantly higher specific RR for TB even after adjusting for the effect of the remaining studied risk factors. Conclusion: The above mentioned factors have to be considered by the clinicians, evaluating for TB in HDPs. Positive TST, the existence of predisposing risk factors and/or old TB lesions on chest X-ray, will guide the diagnosis of latent TB infection and the selection of those HDPs who need preventive chemoprophylaxis.

Prevalence of chronic kidney disease in Thai adults: a national health survey

Leena Ong-ajyooth — 2009-10-31T00:00:00Z

Background: The prevalence of patients with end stage renal disease (ESRD) who need dialysis and/or transplantation has more than doubled in Thailand during the past two decades. It has been suggested that therapeutic strategies to reduce the risk of ESRD and other complications in CKD are now available, thus the early recognition and the institution of proven therapeutic strategies are important and beneficial. We, therefore, aimed to determine the prevalence of CKD in Thai adults from the National Health Examination Survey of 2004. Methods: Data from a nationally representative sample of 3,117 individuals aged 15 years and older was collected using questionnaires, physical examination and blood samples. Serum creatinine was measured by Jaffé method. GFR was estimated using the Chinese modified Modification of Diet in Renal Disease Study equation. Chronic kidney Disease (CKD) stages were classified based on Kidney Disease Outcome Quality Initiative (K/DOQI). Results: The prevalence of CKD in Thai adults weighted to the 2004 Thai population by stage was 8.1% for stage 3, 0.2% and 0.15% for stage 4 and 5 respectively. Compared to non-CKD, individuals with CKD were older, had a higher level of cholesterol, and higher blood pressure. Those with cardiovascular risk factors were more likely to have CKD (stage 3-5) than those without, including hypertension (OR 1.6, 95%CI 1.1, 3.4), diabetes (OR 1.87, 95%CI 1.0, 3.4). CKD was more common in northeast (OR 2.1, 95%CI 1.3, 3.3) compared to central region. Urinalysis was not performed, therefore, we could not have data on CKD stage 1 and 2. We have no specific GFR formula for Thai population. Conclusion: The identification of CKD patients should be evaluated and monitored for appropriate intervention for progression to kidney disease from this screening.

Risk factors for chronic kidney disease in Japan: a community-based study

Norimichi Takamatsu — 2009-10-27T00:00:00Z

Background: Chronic kidney disease (CKD) is increasingly being recognized as a predictor for both end-stage renal disease and cardiovascular disease. The present study, conducted on individuals from a community in Arita, Japan, was designed to evaluate biomarkers that can be used to determine the associated factors for CKD. Methods: This study involved 1554 individuals. Kidney function was evaluated in terms of the creatinine-based estimated glomerular filtration rate (eGFR), which was determined using the Modification of Diet in Renal Disease equation. Low eGFR was defined as eGFR < 60 mL/min per 1.73 m2. The concentration of both urinary albumin and urinary type IV collagen were measured. Results: In the younger participants (age, <65 years), the odds ratio (95% confidence interval [CI]) of low eGFR was 1.17 (1.02 to 1.34) for each 1 year older age, 6.28 (1.41 to 28.03) for urinary albumin creatinine ratio (ACR) over 17.9 mg/g and 9.43 (2.55 to 34.91) for hyperlipidemia. On the other hand, among the elderly participants (age, ≥ 65 years), the odds ratio (95% CI) of low eGFR was 2.97 (1.33 to 6.62) for gender, 1.62 (1.06 to 2.50) for hypertension and 1.97 (1.19 to 3.28) for hyperlipidemia. Urinary type IV collagen creatinine ratio was not identified as an associated factor for low eGFR. Conclusion: In this present cross-sectional community-based study, ACR is associated with CKD, which was defined as an eGFR of less than 60 mL/min per 1.73 m2, in the younger participants but not in the older participants.

Maintaining over time Clinical Performance targets on Anaemia correction in unselected population on chronic dialysis at 20 Italian Centres. Data from a retrospective study for a Clinical Audit

Silvia Soffritti — 2009-10-24T00:00:00Z

Background: The Italian and European Best Practice Guidelines (EBPG) recommend a target haemoglobin value greater than 11 g/dl in most patients with Chronic Kidney Diseases. However, it is still difficult to maintain these values at a steady rate. Thus, the main aim of the study was to evaluate, throughout 2005, how many patients steadily maintained the performance targets related to anaemia treatment. Methods: The survey was conducted on 3283 patients on haemodialysis (HD) and peritoneal dialysis (PD) at 20 Italian dialysis centres. 540 patients were randomly selected; each centre provided a statistically significant sample proportional to its total number of patients. Maintenance of the following target levels was assessed over time: Haemoglobin (HB) 11-12 gr/dl; Iron: 60-160 mcg/dl; Ferritin: 30-400 mcg/l; Transferrin: 200-360 mg/dl; Transferrin saturation percentage (TSAT %):> 25 <50; Dialysis doses (KT/V): >1.2 <2.0 for non-diabetic HD patients; >1.5 <2.2 for diabetic HD patients; DP: >1.8 <2.5.Outcome included:1- Percentage of target maintenance for each parameter.2- Erythropoietin dose in relation to dialysis techniques, presence of cancer or myeloma, diabetic status, Vitamin B therapy.3- Erythropoietin dose (International Units/kg/week) (IU/kg/wk) depending on: haemoglobin values, hospitalization of more than 3 days. Results: Mean age was 65.1; mean haemoglobin concentration over the whole population was 11.3 gr/dl (Standard Deviation (SD): 0.91). The clinical performance targets were maintained over time as follows: HB: 4.3% (Mean 11.43 gr/dl) (SD: 0.42); Ferritin: 71.1% (Mean: 250.23 mcg/L (SD:104.07); Iron: 95.0% (Mean 59.79 mcg/dl)(SD:16.76); Transferrin: 44.8% (Mean 216.83 mg/dl) (SD: 19,50); TSAT %: in 8.4% (Mean: 34.33% (SD: 6.56); HD KT/V: 61.0% (Mean:1.46) (SD: 0.7); PD KT/V:31.4% (Mean: 2.10) (SD: 0.02). The average weekly dose of Erythropoietin (IU/Kg/Wk) was significantly lower for the peritoneal dialysis technique; the higher haemoglobin values, the lower the Erythropoietin dose (IU/Kg/Wk). Conclusion: A very low percentage of patients maintained haemoglobin target values over time. We need to identify precise criteria to evaluate the stability over time of clinical performance targets proposed by the guidelines.

Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients

Ashleigh Reed — 2009-10-22T00:00:00Z

Background: Oxidative stress is associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Although observational data from the general population has shown dietary antioxidant intake is associated with reduced cardiovascular morbidity and mortality, most clinical intervention trials have failed to support this relationship. This may be a consequence of not using an effective antioxidant dose and/or not investigating patients with elevated oxidative stress. The SPACE study, conducted in haemodialysis patients, reported that 800 IU/day of alpha tocopherol significantly reduced cardiovascular disease endpoints. A recent time course and dose response study conducted in hypercholesterolaemic patients that found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose response data available for haemodialysis patients. Therefore the aim of this study is to investigate the effect of different doses of oral alpha tocopherol on oxidative stress in haemodialysis patients with elevated oxidative stress and the time taken to achieve this effect. Methods: The study will consist of a time-course followed by a dose response study. In the time course study 20 haemodialysis patients with elevated oxidative stress will take either 1600 IU/day natural (RRR) alpha tocopherol for 20 weeks or placebo. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma F2-isoprostanes) and alpha tocopherol. The optimum time period to significantly decrease plasma F2-isoprostanes will be determined from this study. In the dose response study 60 patients will be randomised to receive either placebo, 100, 200, 400, 800 or 1600 IU/day of natural (RRR) alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It is hypothesised that doses ≥ 800 IU of vitamin E will be required to significantly decrease plasma F2-isoprostanes.DiscussionThis study will determine the time and dose required for alpha tocopherol to significantly decrease oxidative stress in haemodialysis patients. Data will be used to plan a large randomised controlled trial to assess the effects of alpha tocopherol on cardiovascular outcomes in haemodialysis patients.Trial RegistrationACTRN12609000608268

Chronic kidney disease increases cardiovascular unfavourable outcomes in outpatients with heart failure

Arise Galil — 2009-10-21T00:00:00Z

Background: Chronic heart failure (CHF) has a high morbidity and mortality. Chronic kidney disease (CKD) has consistently been found to be an independent risk factor for unfavorable cardiovascular (CV) outcomes. Early intervention on CKD reduces the progression of CHF, hospitalizations and mortality, yet there are very few studies about CKD as a risk factor in the early stages of CHF. The aims of our study were to assess the prevalence and the prognostic importance of CKD in patients with systolic CHF stages B and C. Methods: This is a prospective cohort study, dealing with prognostic markers for CV endpoints in patients with systolic CHF (ejection fraction ≤ 45%). Results: CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 and CV endpoints as death or hospitalization due to CHF, in 12 months follow-up. Eighty three patients were studied, the mean age was 62.7 ± 12 years, and 56.6% were female. CKD was diagnosed in 49.4% of the patients, 33% of patients with CHF stage B and 67% in the stage C. Cardiovascular endpoints were observed in 26.5% of the patients. When the sample was stratified into stages B and C of CHF, the occurrence of CKD was associated with 100% and 64.7%, respectively, of unfavorable CV outcomes. After adjustments for all other prognostic factors at baseline, it was observed that the diagnosis of CKD increased in 3.6 times the possibility of CV outcomes (CI 95% 1.04-12.67, p = 0.04), whereas higher ejection fraction (R = 0.925, IC 95% 0.862-0.942, p = 0.03) and serum sodium (R = 0.807, IC 95% 0.862-0.992, p = 0.03) were protective. Conclusion: In this cohort of patients with CHF stages B and C, CKD was prevalent and independently associated with increased risk of hospitalization and death secondary to cardiac decompensation, especially in asymptomatic patients.