Correction: Performance of risk prediction scores for cardiovascular mortality in older persons: External validation of the SCORE OP and appraisal

[This corrects the article DOI: 10.1371/journal.pone.0231097.

Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+):Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences

Identifying risk factors for the development of chronic kidney disease in two different populations

Die Anzahl der Patienten mit chronischer Niereninsuffizienz (CNI) wächst weltweit. Da die meist immer noch irreversibel ist, kommt der Präventivmedizin eine immer größere Bedeutung zu. Diese wachsende Bedeutung liegt zum einen in der verkürzten Lebenserwartung und deutlich eingeschränkten Lebensqualität eines Dialysepatienten begründet, zum anderen erleben präventive Strategien vor dem Hintergrund einer immer notwendiger werdenden Kosteneinsparung eine besondere Brisanz. Die Transplantation wird neben den anderen Nierenersatzverfahren i.d.R. als beste Option angesehen, da sie im Vergleich zur Dialyse mit einer höheren Lebenserwartung und verbesserten Lebensqualität einhergeht. Darüber hinaus ist sie trotz teurer Medikamente kostengünstiger als jedes Dialyseverfahren. Wie viel Aufklärung auch bei medizinischem Personal noch notwendig ist, um den wieder wachsenden Spalt zwischen Organangeboten und Wartelistenpatienten zu verkleinern, zeigte unsere Fragebogenerhebung. Das Transplantatüberleben so lange wie möglich zu sichern, ist somit eines der wichtigsten Ziele innerhalb der Transplantations- Nephrologie. Auch hier gilt es, mit Hilfe präventiver Behandlungskonzepte alles zu verhindern, was zu einem Transplantatverlust beitragen könnte. Um präventive Maßnahmen ergreifen zu können, müssen modifizierbare Risikofaktoren identifiziert werden. Die Liste der Ursachen für ein chronisches Nierenversagen wird von Diabetes mellitus (DM) und art. Hypertonie angeführt. Die Rolle der Dys- oder Hyperlipidämie (häufig einhergehend mit DM oder art. Hypertonie) in Verbindung mit „nephrologischen Patienten“, seien sie im Stadium der Prädialyse, Dialyse oder transplantiert, erfährt weiterhin eine kontroverse Diskussion. Besonders im Zusammenhang mit veröffentlichten Daten aus großen RCTs („4D“- u. „ALERT“) konnten unsere beiden Datensätze in Form initial Nierengesunder und Nierentransplantatempfängern dazu beitragen zu verdeutlichen, wie wichtig bezüglich einer Therapieindikation die Differenzierung in verschiedene Populationen ist. So geben, vor dem Hintergrund der Ergebnisse eines marginalen Therapiebenefits durch Statine in der Extension-ALERT-Studie die „Null-Findings“ unserer Untersuchung Anlaß, über eine Kosteneffektivität einer Statintherapie bei NTE nachzudenken. Daß erhöhte Blutfette mit der Entstehung einer Niereninsuffizienz vergesellschaftet sein können, war bisher nicht untersucht worden. Das Ergebnis dieser Analyse ist ein weiteres Argument, Patienten mit erhöhten Blutfetten, v.a. aber auch erniedrigtem HDL, in Hinblick auf die Nierenfunktion großzügig präventiv mit Statinen zu behandeln. Die potentiell protektive Wirkung eines moderaten Alkoholkonsums in Hinblick auf die Entwicklung einer Niereninsuffizienz ist ebenfalls ein neues Ergebnis, welches Aussagen retrospektiver Analysen konterkariert. Gesundheitspolitische Empfehlungen sind diesbezüglich delikat. Inhaltlich sind unsere „Alkohol- protektiven“ Ergebnisse jedoch konsistent, wenn man zum einen die erhöhten HDL-Spiegel bei vermehrtem Alkoholkonsum bedenkt, zum anderen den positiven Effekt sowohl auf die Inzidenz von DM als auch auf die Entwicklung einer Arteriosklerose. Die Untersuchungen von Assoziationen zwischen erhöhtem Calcium, Phosphat und Ca-PO4 und Transplantatüberleben, bzw. Mortalität sind ebenfalls neu und, besonders den Zusammenhang von erhöhtem Calcium und verringertem Risiko betreffend, erstaunlich. Zusammenfassend untersuchten wir in zwei unterschiedlichen Populationen drei potentielle Risikofaktoren, wobei ihre Rolle anhand unserer Analysen teilweise neu interpretiert werden konnte. Wir denken, dass wir somit einen Beitrag zum besseren Verständnis renaler Risikofaktoren liefern konnten, der wiederum helfen kann, den Weg zu ebnen für präventive, zielgerichtete Interventionen.The number of patients with chronic kidney disease (CKD) is growing worldwide. Since CKD is irreversible in most cases, much emphasis should be put on preventive strategies. This growing impact is further emphasized by the shortened life expectancy and limited quality of life in dialysis patients. In terms of cost effectiveness preventive strategies are even more important. Transplantation is seen as one of the best options in renal replacement therapies. Furthermore transplantation is even more cost-effective than other renal replacement therapies such as hemo- or peritoneal-dialysis. Our survey showed how much education is still needed within the medical staff to reduce the widening gap between organ demand and supply. To prolong transplant survival as long as possible and to contribute as much as possible to the best of care for the kidney transplant recipient (KTR) are the most important goals of transplant nephrology. Again preventive strategies are to avoid early and late transplant loss. To take preventive measures modifiable risk factors have to be identified first. The most common causes of CKD are diabetes mellitus (DM) and arterial hypertension. The role of Dys- or Hyperlipidemia (very often associated with DM and hypertension) in the predialysis and dialysis patients or KTR is still discussed in contradictive ways. Especially in the context of recently published huge RCTs (“4D” and “ALERT”) our analyses of initially healthy persons and kidney transplant patients could contribute to demonstrate the importance to differentiate between different populations concerning treatment. In the light of the marginal therapeutic benefit of statins in the extension ALERT-trial our null-findings give reason to think about cost- effectiveness of statins in kidney transplant recipients. The fact that elevated lipid levels can be associated with the development of CKD had not been studied before. The result of this study is another argument to treat patients with elevated lipids and decreased HDL-levels with statins. The potentially protective influence of moderate alcohol intake with regard to CKD-development is a new result too and contradicts former retrospective analyses. Public health recommendations are difficult and should be made with great care. The analyses on associations between elevated Calcium, Phosphate and Ca-PO4-product and transplant survival and mortality respectively are also new and surprising. In summary we investigated three different risk factors in two different populations (initially healthy persons who developed CKD and KTR of whom some developed chronic transplant failure) and were able to interpret their role anew. We think we could contribute to the better understanding of renal risk factors which could help paving the way for preventive strategies

Cardiovascular Risk Factor Control in 70- to 95-Year-Old Individuals: Cross-Sectional Results from the Population-Based AugUR Study

Cardiovascular risk factors such as high glucose, LDL-cholesterol, blood pressure, and impaired kidney function are particularly frequent in old-aged individuals. However, population-based data on the extent of cardiovascular risk factor control in the old-aged population is limited. AugUR is a cohort of the mobile “70+”-year-old population of/near Regensburg, recruited via population registries. We conducted cross-sectional analyses assessing the proportion of AugUR participants with LDL-cholesterol, HbA1c, or blood pressure beyond recommended levels and their association with impaired creatinine- and cystatin-based estimated glomerular filtration rate (eGFR, <60 mL/min/1.73 m2) or urine albumin–creatinine ratio (UACR, ≥30 mg/g). Among 2215 AugUR participants, 74.7% were taking lipid-, glucose-, blood-pressure-lowering, or diuretic medication. High LDL-cholesterol at ≥116 mg/dL was observed for 76.1% (51.1% among those with prior cardiovascular events). We found HbA1c ≥ 7.0% for 6.3%, and high or low systolic blood pressure for 6.8% or 26.5%, respectively (≥160, <120 mmHg). Logistic regression revealed (i) high HbA1c levels associated with increased risk for impaired kidney function among those untreated, (ii) high blood pressure with increased UACR, and (iii) low blood pressure with impaired eGFR, which was confined to individuals taking diuretics. Our results provide important insights into cardiovascular risk factor control in individuals aged 70–95 years, which are understudied in most population-based studies

Development and Validation of Prediction Models of Adverse Kidney Outcomes in the Population With and Without Diabetes.

ObjectiveTo predict adverse kidney outcomes for use in optimizing medical management and clinical trial design.Research design and methodsIn this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or ResultsThere were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts.ConclusionsNovel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR