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In a pre-dialysis population, female gender, cardiovascular disease, malnutrition and inflammation are associated with a higher ESA/Hb index.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

Anaemia is a common finding in elderly patients particularly in those with chronic kidney disease. Effective correction of anaemia improves survival and quality of life. The association between anaemia and a poor nutritional status as well as the presence of inflammation has already been documented. The aim of our study was to assess the impact of the nutritional and inflammatory status on darbepoetin dose requirements of elderly patients followed in a "Chronic Kidney Disease" outpatient clinic. We included 71 elderly patients (age>or=65 years) in a "Chronic Kidney Disease" outpatient clinic. Creatinine Clearance (CrCl) was estimated according to the Cockroft-Gault equation. Nutritional status was evaluated by biochemical and anthropometric parameters. Tumour Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were used as biomarkers of inflammation. Our patients (56% males) with a mean age of 76.2+/-6.6 years were followed for 33.1+/-43.6 months. Mean eCrCl was 13.5+/-7.2 ml/mn/1.73 m2. All patients were under supplemental iron therapy and 74.7% needed darbepoietin (0.762+/-0.6 (microg/kg/week) to correct anaemia. Among the several variables regressed on darbepoietin dose, in a multiple regression model, only Hb, IL-6 and TNF-alpha levels and SGA score predicted the need for higher doses of darbepoietin. (r=0.677; r2=0.459). In Conclusion, in our pre-dialysis elderly patients, markers of a poor nutritional status (SGA and albumin) and inflammation (IL-6 and TNF-alpha) independently predicted the use of higher doses of darbepoietin to correct anaemia.

The increased mortality rate observed in patients with chronic kidney disease is related to the high prevalence of cardiovascular disease in this population. Recently, it has been shown that interventional therapy with statins and/or vitamin D could improve the outcomes of these patients. The aim of this study was to identify the risk factors for mortality in a group of patients with chronic kidney disease (stages 4 and 5--pre-dialysis) and verify whether vitamin D and statins could change the outcome. We included 95 patients (mean age--69.4) with stages 4 and 5 (pre-dialysis) of our "low-clearance" outpatient clinic, with an average eGFR of 16.9 ml/min and a mean follow-up of 24.1 months. Several biological, nutritional, laboratory and inflammatory parameters were analysed at baseline. Our population was divided into three groups: G-I, patients not medicated with either vitamin D or statins; G-II, patients medicated with either vitamin D or statins; and G-III, patients medicated with vitamin D and statins. We found (ANOVA) that the serum levels of pre-albumin (P = 0.018) and PTH (P = 0.03) were lower in G-I. Concerning the inflammatory parameters, G-I showed higher levels of hsCRP (P = 0.014) and a trend to higher IL-6 levels (P = 0.077). We found the actuarial survival at 30 months (Kaplan-Meier), to be 56.4% in G-I, 82.3% in G-II and 100% in G-III (log rank = 13.08 P = 0.0014). Using the Cox proportional hazards model, we found that the existence of coronary artery disease (P = 0.0001) and the absence of medication with vitamin D and/or statins (P = 0.005) independently influenced the mortality of our patients. In conclusion, we found, in our study, that patients under vitamin D and statins (with a synergistic effect) were less inflamed and showed a lower mortality rate.

Anaemia and hypertension are common in patients with chronic renal insufficiency. The correction of anaemia with erythropoiesis stimulating agents (ESA) can improve survival and decrease the decline of renal function. Angiotensin converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (AIIRA) can also slow the progression of renal failure, but the blockade of the renin-angiotensin system can worsen anaemia. The aim of our study was to assess the impact of antihypertensive therapy (ACEI plus AIIRA) in the requirements of darbepoietin in a group of elderly predialysis patients. We included 71 patients (m = 39, f = 32), mean age of 76.3 years with a mean creatinine clearance of 17.5 ml/min. Patients were divided in two groups according to their antihypertensive therapy: G-I patients under ACEI or AIIRA therapy and G-II normotensive patients or hypertensive patients under antihypertensive drugs other than ACEI or AIIRA. The groups were compared regarding demographic, nutritional, biochemical and inflammatory parameters. We also compared the mean darbepoietin dose. In GI the mean dose of darbepoietin was higher than in GII (0.543 vs. 0.325 microg/kg/week, P = 0.032). We did not find any difference regarding other parameters analysed. We conclude that ACEI and AIIRA can increase the needs of darbepoietin in predialysis elderly patients. However, when formally indicated to treat hypertension in a specific patient, they should not be switched to another antihypertensive agent. Instead, in such cases, higher doses of ESA should be used, if necessary.

BACKGROUND: Various classical risk factors are associated with the progression of chronic kidney disease (CKD) and, recently, novel risk factors have been identified. The aim of this study was to identify factors associated with the risk of end-stage renal disease (ESRD) in a population of patients with CKD stages 4 and 5. METHODS: We prospectively followed renal patients at our clinic (mean glomerular filtration rate [GFR] of 16.9 mL/min) for an average of 12.4 months. The end point was initiation of dialysis. For comparisons between groups, we used Student's t-and χ 2 tests. Using the Cox proportional hazard model, we regressed several independent variables on time to dialysis. We also evaluated the influence of IL-6 on the progression of CKD, using the Kaplan-Meier method.RESULTS: Ninety-five patients (54 men; mean age, 69.4 years) participated in the study. A greater proportion of those who began dialysis were male (p ϭ 0.003). Their GFR (p ϭ 0.0001), hemoglobin (p ϭ 0.024), and the albumin (p ϭ 0.034) levels were lower and their IL-6 was higher (p ϭ 0.002) than those who did not begin dialysis. We also found that male sex (p ϭ 0.001), hypertension (p ϭ 0.043), lower GFR level (p ϭ 0.018), lower hemoglobin level (p ϭ 0.039), and higher IL-6 level (p ϭ 0.0001) predicted faster progression to ESRD. Patients whose IL-6 levels were in the upper quartiles had lower kidney survival after 12 months (log rank ϭ 35.1, p ϭ 0.0001).CONCLUSION: In our population, anemia and interleukin-6 were associated with faster progression to ESRD.

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