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

Evaluation of the value of albuminuria in the diagnosis and prognosis of nephropathy in type 2 diabetics with renal insufficiency

In der nephrologischen Praxis werden oft Typ 2 Diabetiker mit chronisch eingeschränkter Nierenfunktion behandelt. Die vorliegenden Arbeit soll einen Beitrag leisten in der Bewertung der prognostischen Bedeutung eine Albuminurie von <20 mg/l bei Typ 2 Diabetikern mit einer eGFR unter 60 ml/min. Im Rahmen einer regionalen offenen Kohortenbeobachtungsstudie wurden 332 Typ 2 Diabetiker konsekutiv untersucht, die von ihren Hausärzten im Zeitraum von März 1998 bis März 2007 erstmalig zur nephrologischen Mitbehandlung einer Niereninsuffizienz in das Nierenzentrum Berlin-Köpenick überwiesen wurden. 39 Patienten, die nicht mit einem ACE-Hemmer oder einem ATRB (Angiotensin Rezeptor Blocker) vorbehandelt waren, wurden von der weiteren Auswertung ausgeschlossen; ebenso 16 Patienten, bei denen eine Nierenarterienstenose diagnostiziert wurde. Von den verbleibenden 277 Patienten hatten 95 eine nur leichte Einschränkung der Nierenfunktion (Stadium 2) mit einer eGFR zwischen 60 und 90 ml/min und wurden überwiegend hausärztlich weiterbetreut. Bei 182 Patienten lag eine Niereninsuffizienz mit einer eGFR unter 60 ml/min vor. Von diesen 182 Patienten konnten 164 über einen medianen Zeitraum von 35 Monaten hinsichtlich des Auftretens von renalen und kardiovaskulären Komplikationen nachbeobachtet werden. Bei den 164 Typ 2 Diabetiker mit einer eGFR unter 60 ml/min, bestand bei 107 Patienten eine Mikro- oder Makroalbuminurie (Mikroalbuminurie von 0,02 bis <0,2g/l: 50 Patienten, Albuminurie von 0,2 bis 1,0 g/l: 32 Patienten, Albuminurie > 1 g/l: 25 Patienten). Bei 57 Patienten fand sich eine Albuminurie <20 mg/l. Im Verlauf der Nachbeobachtung erreichten 19 der 164 Patienten (12 %) den renalen, 47 Patienten (29 %) einen kardiovaskulären und Endpunkt und 28 Patienten verstarben (17 %). Von den 107 Diabetikern mit Albuminurie verstarben 17 (16 %), davon 9 (53 %) an kardiovaskulären Komplikationen. Von den 57 Diabetikern mit Albuminurie <20 mg/l verstarben 11 (19 %), davon 9 (82 %) an kardiovaskulären Komplikationen. Sie erreichten den kardiovaskulären Endpunkt signifikant öfter und schneller. Niereninsuffiziente Diabetiker mit Albuminurie <20 mg/l waren somit in unserm Kollektiv hinsichtlich kardiovaskulärer Komplikationen als Hochrisikopatienten mindestens ebenso gefährdet wie Patienten mit Albuminurie ≥20 mg/l. Den renalen Endpunkt erreichte einer von 57 Patienten (2 %) mit Albuminurie <20 mg/l gegenüber 18 von 107 Patienten (17 %) mit Albuminurie ≥20 mg/l. Die schlechteste Gesamtprognose hatten die 25 Diabetiker mit einer Albuminurie über 1 g/l. Jeder Dritte von ihnen verstarb, 42 % erreichten den renalen und 28 % den kardiovaskulären Endpunkt. Somit konnte gezeigt werden, dass bei Patienten mit einer Albuminurie <20 mg/l einerseits die renale Prognose im Untersuchungszeitraum gut war, andererseits aber ein überdurchschnittliches kardiovaskuläres Risiko bestand.Type 2 diabetics with chronically reduced renal function often receive nephrological care. This work endeavours to contribute to the evaluation of the prognostic significance of albuminuria <20 mg/L in type 2 diabetics with an eGFR below 60 mL/min. As part of a regional open observational study, 332 type 2 diabetics were examined consecutively, who had been referred for the first time by their family physicians for nephrological treatment of their renal insufficiency to the KfH Kidney Centre Berlin-Köpenick between March 1998 and March 2007. 39 patients not pre-treated with an ACE inhibitor or an ATRB (angiotensin receptor blocker) were excluded from further evaluation, as were 16 patients, in whom a renal artery stenosis was diagnosed. Of the remaining 277 patients, 95 had only mild impairment of renal function (stage 2) with an eGFR between 60 and 90 mL/min and predominantly received continuing care by their family physicians. 182 patients had renal insufficiency with an eGFR below 60 mL/min. Of these 182 patients, 164 were followed up over a median period of 35 months for the occurrence of renal and cardiovascular complications. In the 164 type 2 diabetics with an eGFR below 60 mL/min, 107 patients had a micro- or macroalbuminuria (microalbuminuria from 0.02 to <0.2g/L in 50 patients, albuminuria from 0.2 to 1.0 g/L in 32 patients, and albuminuria > 1 g/L in 25 patients). 57 patients had albuminuria <20 mg/L. During follow-up, 19 of the 164 patients (12%) reached the renal endpoint, 47 patients (29%) the cardiovascular endpoint, and 28 patients died (17%). Of the 107 diabetics with albuminuria, 17 (16%) died, of whom 9 (53%) died of cardiovascular complications. Of the 57 diabetics with albuminuria <20 mg/L, 11 (19%) died, of whom 9 (82%) died of cardiovascular complications. They reached the cardiovascular endpoint significantly more frequently and faster. Therefore, in our study population diabetics with renal insufficiency and albuminuria <20 mg/L were at the same high risk of cardiovascular complications as patients with albuminuria ≥20 mg/L. One of the 57 patients (2%) with albuminuria <20 mg/L reached the renal endpoint compared with 18 of the 107 patients (17%) with albuminuria ≥20 mg/L. The 25 diabetics with albuminuria over 1 g/L had the worst overall prognosis. One third of them died, 42% reached the renal and 28% the cardiovascular endpoint. It was thus possible to show that while patients with albuminuria <20 mg/L had a good renal prognosis during the study period, their cardiovascular risk was above average

Predicting Kidney Failure, Cardiovascular Disease and Death in Advanced CKD Patients

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries

Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD

Background: Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks.Methods: To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration.Results: The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts.Conclusions: Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years)

The association between TMAO, CMPF and clinical outcomes in advanced CKD; results from the EQUAL study

Background Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source. Objectives We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes. Methods Patients were recruited from the European QUALity (EQUAL) Study on treatment in advanced chronic kidney disease among individuals aged &gt;= 65 y whose estimated glomerular filtration rate (eGFR) had dropped for the first time to &lt;= 20 mL/min per 1.73 m(2) during the last 6 mo. The association between TMAO, CMPF, and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cutoffs of TMAO and CMPF, suggesting high/low red meat and fish intake. Results During a median of 39 mo of follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable HR: 1.46; 95% CI: 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR: 0.79; 95% CI: 0.71, 0.89) and KRT (HR: 0.80; 95% CI: 0.71, 0.90), independently of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR: 0.49; 95% CI: 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models. Conclusions High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF concentrations are due to fish consumption, and/or if CMPF is a protective factor, remains to be verified

Symptom Burden before and after Dialysis Initiation in Older Patients

For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients