Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

[Iron deficiency in ND-CKD: from diagnosis to treatment]

In non-dialysis-chronic kidney disease (CKD), iron deficiency is a frequent nutritional disorder due to either the greater tendency to occult gastrointestinal bleeding or to the chronic inflammatory state resulting in a reduced intestinal iron reabsorption through an increased synthesis of hepcidin. These phenomenon are responsible for a negative iron balance that compromises erythropoiesis and contributes to the pathogenesis of anemia in CKD. Several laboratory tests are now available to allow an adequate diagnosis of iron deficiency. Among the new parameters, the percentage of hypochromic red cells (% HYPO) and the reticulocyte hemoglobin content (CHr) are now considered as the most specific markers for diagnosing iron-deficiency erythropoiesis. Unfortunately, their implementation in clinical practice is limited by the scarce availability. In non-dialyzed CKD , subjects intolerant or non-responsive to oral iron therapy, can be effectively treated with novel intravenous iron preparations, such as iron carboxymaltose, that allow a complete and rapid correction of iron deficient anemia. Furthermore, this iron compound is associated with lower rate of adverse effects since the carbohydrate shell (carboxymaltose) is more stable than gluconate and saccarate thus reducing the release of free iron in the bloodstream. Of note, the possibility of administering this drug at high doses and reduced frequency decreases the risk of infusion reactions. Finally, a substantial economic saving mainly dependent on a reduction in indirect costs represents a further advantage in the use of iron carboxymaltose in this population

[Epidemiology and prognosis of chronic kidney disease in Italy]

Because chronic kidney disease (CKD) is a major public health issue, it is important to make the available epidemiological data widely known for a proper understanding of its social impact, and to identify risk factors that can influence the prognosis of the disease. The data from the CARHES study show in the general population of Italy a prevalence of CKD (stage 1-5) of 8%, less than in other countries, a higher prevalence of proteinuria at early stages (1-2), and a cardiovascular risk profile in CKD patients characterized by metabolic syndrome. The prognosis of CKD is an essential element in clinical practice as it allows to better define the severity of the disease and to determine the most appropriate therapeutic approach. The data from the TABLE study, performed in nephrology care, show that ESRD was more frequent than death before dialysis but not in stage 3; we note that advanced age reduces the progression of renal failure and that the most important among the modifiable risk factors is proteinuria, which has a negative predictive role in stage 3-4 but not stage 5 and which interacts specifically with advanced age. No predictive role was found for hypertension, but this is only apparently surprising; in fact, there is growing evidence of the superior effectiveness of ambulatory blood pressure measurement (ABPM) over office blood pressure measurement. These data, together with the results of some trials, show the need for the more extensive use of ABPM to identify subjects with white-coat hypertension and to better control the circadian blood pressure profile by administering antihypertensive drugs also in the evening

Nephroprotection with saxagliptin

The nephroprotective effect of the new anti-diabetic drugs acting on incretin system is suggested by preclinical studies. However, no study evaluating kidney effects of these drugs as primary outcome on the long term has been conducted in patients followed in diabetes centers. We designed a pilot observational study involving two diabetes clinics to evaluate the effect of prolonged treatment with saxagliptin on renal function in type 2 diabetics. Patients were enrolled if treated for at least 12 months with saxagliptin without concurrent changes to anti-hypertensive and lipid-lowering therapy. Primary outcome was to evaluate the effect of saxagliptin on albuminuria and estimated glomerular filtration rate (eGFR). Secondary outcomes were the effects of treatment on common clinical and laboratory parameters. Sixty-three patients were enrolled. After 12 months of treatment with saxagliptin, albuminuria declined from a mean (95%CI) of 39 (25-52) to 22 (14-30) mg/l (P<0.001), and the prevalence of increased albuminuria (>20 mg/L) diminished by 27% versus baseline. The anti-albuminuric effect was independent of glycemic and blood pressure control. The eGFR remained unchanged after treatment in the presence of decreased glycated hemoglobin (from 7.1 to 6.7%). Therefore, this pilot study suggests that saxagliptin treatment in diabetic patients at high renal risk is associated with a reduction in albuminuria and GFR stability. Prospective trials are required to confirm the potential nephroprotective effects of saxagliptin

[Clinical experience with ferric carboxymaltose in non-dialysis chronic kidney disease]

Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often show anemia and iron deficiency despite oral iron supplementation caused by poor iron absorption, intolerance and non-compliance

Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care

<div><p>Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤130/80 mmHg in patients with proteinuria ≥150 mg/24h and/or diabetes and ≤140/90 in those with proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb ≥11 g/dL), and proteinuria (≤0.5 g/24h). Survival analysis started after first year of nephrology care. We studied 729 patients (age 64±15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28–10.6) and DN (1.28,2.99–3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk factors to refine renal risk stratification.</p></div

Therapy at baseline and month-12 visit.

<p>Data are mean±SD or % of patients and (95%CI). RAS, renin-angiotensin system; BP, blood pressure; LSD, low salt diet (UNaV <100 mmol/24h); ESA, erythropoiesis stimulating agents.</p><p>* P<0.05 versus baseline</p><p>Therapy at baseline and month-12 visit.</p

Control of main modifiable factors at baseline and month-12 visit.

<p>Data are % of patients and (95%CI). BP, blood pressure (mmHg); Hb, hemoglobin (g/dL); Uprot, proteinuria (g/24h).</p><p>* P<0.05 versus baseline.</p><p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127071#sec002" target="_blank">Methods</a> for definition of goal values</p><p>Control of main modifiable factors at baseline and month-12 visit.</p

Multivariable Cox models of determinants of the combined renal endpoint.

<p>Model 1: diagnoses and goals are separately adjusted for main covariates (age, gender, history of CV disease, BMI, eGFR, use of RAS inhibitors). Model 2: fully adjusted (adjusted for main covariates of model 1 plus diagnoses and therapeutic goals). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127071#sec002" target="_blank">Methods</a> for definition of goal values. HTN, hypertensive nephropathy; DN, diabetic nephropathy; GN, glomerulonephritis; PKD, autosomal polycystic kidney disease; TIN, tubulointerstitial nephropathy. R²R, R² reduction.</p><p>Multivariable Cox models of determinants of the combined renal endpoint.</p

Cumulative incidence after month-12 visit of renal event (panel A) and all-cause death before ESRD (panel B).

<p>Cumulative incidence after month-12 visit of renal event (panel A) and all-cause death before ESRD (panel B).</p