[Chronic kidney dysfunction in the elderly patient: physiological process or disease?]. / Disfunzione renale nell'anziano: processo fisiologico o malattia?

The last few years have seen a steady rise in numbers of patients with chronic kidney disease (CKD), mainly because of the increased prevalence of older patients. Today, most new diagnoses of CKD are made in patients belonging to the large subgroup of subjects aged 65 years or over, who often present with mild-to-moderate CKD. Given the recent rise in numbers of elderly CKD patients referred to American renal clinics, the American Society of Nephrology has recently endorsed a study group dedicated to this group of patients, Geriatric Nephrology, with the aim of increasing knowledge on CKD in the elderly and subsequently improving the clinical management of older patients. Indeed, several questions remain open and further studies are required to clarify diagnostic criteria for 'true' CKD in the elderly and the associated 'real' clinical implications in terms of hard outcomes. This review aims to address a hot topic through evaluation of the most recent and influential studies regarding the relationship between ageing and CKD.

Therapy of hyperhomocysteinemia in hemodialysis patients: effects of folates and N-acetylcysteine.

OBJECTIVE: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. DESIGN: The study is an open, parallel, intervention study. SETTING: Ambulatory chronic hemodialysis patients. SUBJECTS: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). INTERVENTION: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). MAIN OUTCOME MEASURE: Plasma homocysteine measured before and after dialysis at the first and the last treatment. RESULTS: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 µmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 µmol/L, compared with 19% in the MTHF group and 16% in the control group. CONCLUSIONS: NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration.

Stability of target hemoglobin levels during the first year of epoetin treatment in patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Instability of hemoglobin levels during epoetin therapy is a new problem in hemodialysis. We evaluated extent and correlates of time in target, that is, the time spent with hemoglobin > or = 11 g/dl during the first year of epoetin and its association with renal survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were collected in 917 visits for 12.0 mo in 119 patients with chronic kidney disease; thereafter, patients started renal survival analysis for 10.1 mo. At baseline, hemoglobin was 10.0 +/- 0.8 g/dl and GFR was 22.1 +/- 14.2 ml/min per 1.73 m2. RESULTS: Hemoglobin target, reached in 1.5 mo, was steadily maintained in only 24% of patients. Time in target was not merely due to differences in time to target; after first achievement of target, in fact, a reduction of hemoglobin < 11 g/dl occurred in 51% of patients. At multivariate analysis, male gender, basal GFR and hemoglobin levels, first epoetin dose, and iron supplementation were directly associated with length of time in target. A lower risk for renal death (dialysis n = 53; death n = 8) was detected in the higher tertile of time in target (11.3 mo) versus lower tertile (3.2 mo). This difference persisted at Cox analysis after adjustment for age, gender, GFR, BP, and proteinuria. CONCLUSIONS: In chronic kidney disease, time in target during the first year of epoetin therapy is frequently short depending not only on time to target but also on post-target hemoglobin reductions, correlates with male gender, timing, and intensity of initial therapy and is coupled with better renal survival.

Management of cardiovascular risk factors in advanced type 2 diabetic nephropathy: a comparative analysis in nephrology, diabetology and primary care settings.

OBJECTIVES: Advanced diabetic nephropathy (DN) is characterized by a marked development of cardiovascular and renal disease. These patients are frequently managed by different health professionals with the consequence that the quality of care may differ substantially. To compare the management of cardiovascular risk factors in patients with type 2 DN and an estimated glomerular filtration rate (GFR) of 15-60 ml/min per 1.73 m2 followed in nephrology, diabetology and primary care. METHODS: This multicentre cross-sectional study verified the control of blood pressure (BP), total cholesterol, triglycerides, glycosylated haemoglobin A1c (HbA1c) and haemoglobin in patients exclusively followed in either nephrology (n = 266), diabetology (n = 246) or primary care (n = 195) of the same metropolitan area for at least 1 year. RESULTS: Primary care patients were older and had a greater prevalence of previous cardiovascular events. The GFR was lower in nephrology than in diabetology and primary care (33 +/- 13 versus 47 +/- 9 and 40 +/- 12 ml/min per 1.73 m2, P < 0.0001). The prevalence of BP target (< 130/80 mmHg) was similarly low in nephrology, diabetology and primary care (14, 13 and 10%, P = 0.421) probably because of insufficient prescription of diuretics and low-salt diet. Whereas the prevalence of the triglycerides target was similar, that of total cholesterol (< 200 mg/dl) was larger in diabetology (63%) than in nephrology and primary care (59 and 46%, P = 0.003) because of greater statin prescription in hypercholesterolemic individuals (70, 50 and 41%, respectively, P = 0.002). The attainment of HbA1c less than 7% was less frequent in diabetology (32%) than in nephrology and primary care (61 and 46%, P = 0.0003) despite a more frequent prescription of insulin/oral agents in diabetology. The control of anaemia was better in diabetology. Multivariate analysis adjusted for the patient case-mix and physician-level clustering confirmed these differences except for anaemia. CONCLUSION: Patients with advanced DN, despite the worst renal and cardiovascular prognosis, are at high risk of being under-treated independently of the type of clinical setting.

T-lymphocyte populations and cytokines in childhood nephrotic syndrome.

We investigated lymphocyte subpopulations and the production of cytokines by T helper cell subtype 1 (Th1), Th2, and monocytes/macrophages (tumor necrosis factor-alpha [TNF-alpha]) in peripheral-blood mononuclear cells of 18 children with steroid-sensitive (SS) nephrotic syndrome (NS) and 10 children with steroid-resistant (SR) NS. Mean age was 10.9 +/- 5.7 years, with a mean follow-up before the study of 6 +/- 5 years. To evaluate the possible relationship between cytokine levels and response to treatment, patients with SS and SR NS were assessed during relapse/marked proteinuria (group A), total/partial remission (group B), and off treatment (group C). In children with SS and SR NS, we found no significant difference in CD3 counts compared with controls. The proportion of CD4 cells decreased significantly in relapse and off therapy compared with controls in children with SS NS, whereas in those with SR NS, there was a concomitant reduction in all groups. B-Lymphocyte counts were significantly increased in either group versus controls. In SR NS, CD8 and natural killer cell levels increased during relapse versus controls. The CD4+/CD8+ ratio was reduced to the same degree in those with SS and SR NS. In patients with SR NS, we observed increased levels of soluble interleukin-2 (IL-2) receptor (sIL-2R) from corresponding control values (P < 0.01). A significant increase in TNF-alpha levels was found in patients with SS and SR NS versus controls. High levels of IL-2, sIL-2R, and interferon-gamma during relapse in patients with SS NS give further evidence for a Th1 pattern that might be involved in the pathogenesis of NS, and monitoring the Th1/Th2 balance would be useful in evaluating the response to therapy.