Kidney Disease: Improving Global Outcomes Classification Research Articles

Risk factors for chronic kidney disease in middle eastern patients with type 2 diabetes mellitus: A cross-sectional study using the KDIGO classification

AimsChronic kidney disease (CKD) is prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate risk factors for CKD progression across the kidney disease-Improving Global Outcomes (KDIGO)categories in a Middle Eastern population beyond hyperglycemia as emphasized by KDIGO guidelines which classifying CKD by cause and severity. MethodsThis cross-sectional study targeted 1603 patients with T2DM. Risk factors for CKD progression were determined using odds ratios (ORs) and 95 % confidence intervals (CIs). ResultsOverall, 35.5 %, 31.7 %, and 32.8 % of patients were classified as low-risk, moderate-risk, and high-/very high-/highest-risk, respectively. Several factors were associated with high/very high/highest risk categorization, including being aged >45 years (OR: 1.85, 95 % CI: 1.36–2.49; P < 0.001), male gender (OR: 1.87, 95 % CI: 1.38–2.54; P < 0.001), hypertension (OR: 3.66, 95 % CI: 2.32–5.78; P < 0.001), and T2DM duration of ≥15 years (OR: 3.2, 95 % CI: 2.27–4.5; P < 0.001). Patients with more concurrent risk factors were notably represented in the high/very high/highest risk category. ConclusionsMale patients, older patients, and those with comorbid hypertension, longstanding T2DM, and additional concurrent risk factors have a significantly higher risk of advanced CKD. Such findings should be considered when planning management approaches for patients with CKD.

The relationship of KDIGO classification and incidence &amp; mortality of acute kidney injury in sepsis patients in intensive care unit: A retrospective cohort study

Background/Aim: Acute kidney injury (AKI) is a common and serious complication associated with morbidity and mortality in patients with sepsis. This study aimed to determine the severity of AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and evaluate its relationship with mortality in patients who were followed up in the intensive care unit (ICU) due to sepsis and developed AKI. Methods: We retrospectively analyzed patients diagnosed with sepsis and followed up in the ICU, including all patients with AKI. The severity of AKI was determined for all patients using the KDIGO criteria. The patients were divided into four groups: Stage 1, Stage 2, Stage 3, and without AKI. Patients with missing data, COVID-19 patients, patients with chronic kidney insufficiency, and kidney transplant patients were excluded. Results: A total of 1,177 sepsis patients were included in the study, of whom 52.4% were male (n=617). The median age of the study group was 78 years (Q1-Q3: 68-85 years). It was determined that 57.9% of the patients (n=681) developed AKI at any stage. According to the KDIGO criteria, the rates of patients in Stage 1, Stage 2, and Stage 3 developing AKI were 23.9%, 16.2%, and 17.8%, respectively. The incidence of hypertension (HT) and diabetes mellitus (DM), which are comorbidities, increased as the patients’ KDIGO stage increased (P&lt;0.001). Conclusion: AKI occurred in 57.9% of sepsis patients in the ICU, and 30.4% received renal replacement therapy (RRT). It was determined that mortality increased as the KDIGO stage of our patients increased.

Acute Kidney Injury Classifications in the Prediction of In-hospital Mortality and Renal Function Non-recovery.

In the last two decades diagnostic criteria for acute kidney injury (AKI) were developed: Risk, Injury, Failure, Loss of Kidney Function, End-Stage Kidney Disease (RIFLE), Acute Kidney Injury Network (AKIN), and Kidney Disease: Improving Global Outcomes (KDIGO) classifications. The study aimed to determine the incidence of AKI based on the RIFLE, AKIN, and KDIGO criteria, as well as analyze their predictive value for mortality and renal function outcome. This was a single-center prospective study of patients diagnosed with AKI. Acute kidney injury was defined and classified according to the RIFLE, AKIN, and KDIGO criteria. The outcomes were renal function outcome and in-hospital mortality. The incidence rates of AKI based on the RIFLE, AKIN, and KDIGO criteria were 13.4%, 14-36%, and 14.64%, respectively. Multiple regression analysis showed that higher stages of AKI according to the KDIGO criteria were independently associated with non-recovery of renal function (p=0.011). However, the predictive ability of RIFLE, AKIN and KDIGO classifications for renal function recovery was poor (Area Under the Receiver Operating Characteristics-AUROC=0.599, AUROC=0.637, AUROC=0.659, respectively). According to the RIFLE and AKIN criteria, in-hospital mortality was statistically significantly higher in stage Failure/3 (p=0.0403 and p=0.0329, respectively) compared to stages Risk/1 and Injury/2. Receiver Operating Characteristics (ROC) analysis showed that all three classifications had poor predictive ability for in-hospital mortality (AUROC=0.675, AUROC=0.66, AUROC=0.681). KDIGO classification is an independent predictor of renal function non-recovery. However, by ROC analysis, all three classifications have poor predictive ability for renal function outcome and mortality.

Risk factors of chronic kidney disease among type 2 diabetic patients with longer duration of diabetes.

Chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) is the major cause of end stage renal disease, characterized by proteinuria with a subsequent decline in glomerular filtration rate. Although hyperglycemia is the major risk factor for the development and progression of kidney disease among diabetic patients, many other risk factors also contribute to structural and functional changes in the kidneys. As recommended by Kidney Disease Improving Global Outcomes (KDIGO), CKD classification based on cause and severity, links to risk of adverse outcomes including mortality and kidney outcomes. The aim of this study is to investigate the involvement of risk factors associated with the severity of CKD among participants with longer duration of diabetes. This study also aims to find whether number of risk factors vary among risk of CKD progression categories based on KDIGO classification. This cross-sectional study retrospectively selected 424 participants from type 2 diabetic cohort and categorized them based on the classifications for the diagnosis of kidney diseases in patients with diabetes, according to the KDIGO guidelines. Odds ratios and 95% CI of each risk factors according to severity of renal disease were determined. Based on KDIGO classification, participants with type 2 diabetes (T2D) were categorized in to low risk (n=174); moderately increased risk (n=98); and high/very high risk (n=152). Type 2 diabetic participants with risk factors such as, hyperlipidemia, hypertension, DM duration ≥15 years and diabetic retinopathy showed a high/very high risk of CKD progression when compared with low-risk category. While T2D participants with risk factors such as, lack of exercise, hypertension, and diabetic retinopathy showed a moderately increased risk of CKD progression. In addition, participants with highest number of risk factors were significantly distributed among high/very high risk of CKD progression category. This study findings conclude that patients with T2DM and duration of ≥15 years, hyperlipidemia, hypertension and diabetic retinopathy have an increased prevalence of advanced CKD. In addition to this, increased number of risk factors could be an indicator of the severity of CKD in T2D.

Abstract 126: The Association Of Higher Or Lower Mean Arterial Pressure On Kidney Function After Cardiac Arrest: A Post-hoc Analysis Of The Comacare And Neuroprotect Trials

Introduction: Acute kidney injury (AKI) denotes a sudden reduction in kidney function manifested by a rise in S-creatine levels and reduced urine output. Studies have suggested an association between AKI severity and outcomes after OHCA. Various criteria have been used to define AKI, the Kidney Disease Improving Global Outcomes (KDIGO) published in 2012 being the currently used tool. AKI is a feature of post-cardiac arrest syndrome.During post-CA syndrome, possible causes of renal damage are direct renal ischaemic-reperfusion injury and indirect renal damage characterized by the activation of inflammatory and coagulation pathways. Although the overall mortality rate after CA mainly relates to hypoxic-ischaemic brain injury, damage to other organs also has prognostic implications. Methods: Pooled post-hoc analysis of the COMACARE (NCT02698917) and NEUROPROTECT (NCT02541591) trials that randomized patients to lower (MAP 65-70 mmHg) or higher (MAP 80-100 mmHg) targets for the first 36 hours of post-CA intensive care. Kidney function was categorised using the KDIGO classification during the first five days after OHCA. We used Cox regression analysis to identify factors associated with AKI after OHCA. Results: A total of 227 patients were included: 115 in the high MAP group and 112 in the low MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 (47%) patients had AKI in the high MAP group and 46 (54%) in the low MAP group (p = 0.51). The mean creatinine and mean daily diuresis were 104 (95% CI 94-115) μmol/l and 1989 (95% CI 1829-2150) mL/day in the high MAP group and 111 (95% CI 99-122) μmol/l and 1677 (95% CI 1530-1824) mL/day in the low MAP group. In a Cox regression model, independent AKI predictors were previous hypertension (HR 1.72; 95% CI 1.07-2.78; p = 0.03), bystander cardiopulmonary resuscitation (hazard ratio [HR] 0.46; 95% CI 0.29-0.73; p &lt; 0.01), shockable initial rhythm (HR 0.36; 95% CI 0.21-0.61; p ≤ 0.01), and time to ROSC (HR 1.04; 95% CI 1.02-1.06; p &lt; 0.01) whereas high/low MAP was not an independent predictor of AKI. Conclusions: KDIGO1-staged AKI is common after CA and is associated with previous hypertension and CA factors. Targeting higher MAP after CA does not appear to influence the development of AKI.

Efficacy of empagliflozin in patients with heart failure according to baseline KDIGO risk categories – findings from the EMPEROR-Pooled

Abstract Background and objective Chronic kidney disease (CKD) is common in patients with heart failure (HF) and is associated with an incrementally higher risk for mortality and morbidity. EMPEROR-Pooled studied 9,718 HF patients across two trials and showed that empagliflozin reduces the risk for HF hospitalization or cardiovascular (CV) death, slows the progression of estimated glomerular filtration rate (eGFR) decline, and improves health status in patients with HF and reduced ejection fraction (HFrEF) as well as preserved ejection fraction (HFpEF). Purpose We explored the effect of empagliflozin on CV and kidney endpoints in patients across KDIGO (Kidney Disease Improving Global Outcomes) risk categories in EMPEROR-Pooled. Methods 3,730 participants with left ventricular EF ≤40% (EMPEROR-Reduced) and 5,988 with left ventricular EF &amp;gt;40% (EMPEROR-Preserved) were categorized using baseline eGFR and UACR values into 4 categories according to KDIGO classification. The key outcomes were (1) a composite of CV death or hospitalization for HF, (2) first hospitalization for HF, (3) CV death and (4) eGFR slope change/year. Results The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 31.4%, 29.6%, 22.0%, 16.9% for empagliflozin and 32.5%, 28.4%, 21.8%, 17.2% for placebo, respectively. Patients on placebo in higher baseline KDIGO risk categories had a higher risk of CV death or hospitalization for HF (6.78, 11.30, 15.15, and 20.70 events per 100 patient-years for low-, moderate-, high-, and very high-risk patients, respectively) (Figure 1). Similar trends were seen for first HF hospitalization (4.46, 7.68, 11.14, and 15.98 per 100 patients-years at risk) and CV death (2.98, 5.31, 5.69, and 7.60 per 100 patients-years at risk). eGFR slope decreased less in higher baseline KDIGO risk categories (−3.13 in low-, −2.81 in moderate-, −2.17 in high- and −1.61 ml/min/1.73 m2 per year in very high-risk category) (Figure 2). Empagliflozin reduced the risk of CV death or hospitalizations for HF similarly across KDIGO risk categories (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.66, 1.01 for low-, HR 0.63; 95% CI 0.52, 0.76 for moderate-, HR 0.82; 95% CI 0.68, 0.98 for high- and HR 0.84; 95% CI 0.71, 1.01 for very high-risk group; P trend=0.299). Similarly, empagliflozin reduced the risk of first HF hospitalization (P trend=0.186), CV death (P trend=0.663) or eGFR slope change (P trend=0.069) across the four groups. Conclusions Treatment with empagliflozin reduced the risk for CV death or HF hospitalization and slowed the rate of kidney function decline similarly in all KDIGO CKD risk categories. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim &amp; Eli Lilly and Company Diabetes Alliance

Blood pressure variability and early neurological deterioration according to the chronic kidney disease risk categories in minor ischemic stroke patients.

Chronic kidney disease (CKD) increases blood pressure variability (BPV) and affects stroke outcomes. However, the effect of BPV on early neurological deterioration (END) may be different according to the renal function. We enrolled ischemic stroke patients with a National Institutes of Health Stroke Scale of ≤5. END was defined as worsening of ≥1 point in motor power or ≥2 points in total score. BPV was calculated with BP measured during the first 5 days and presented as standard deviation (SD) and coefficient of variation (CoV). Renal function was classified using the Kidney Disease Improving Global Outcomes (KDIGO) classification of CKD. Variables were compared between those with (KDIGO classification: moderate- to very-high-risk) and without renal impairment (KDIGO classification: low-risk) and factors associated with END were investigated. Among the 290 patients (136 [46.9%] renal impairment), END was observed in 59 (20.3%) patients. BPV parameters and the risk of END increased as renal function was impaired. Renal function and systolic BP (SBP) mean, SD, CoV, and diastolic BP (DBP) mean, SD were independently associated with END. We found no association between BPV parameters and END in normal renal function patients; however, among impaired renal function patients, SBP SD (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.09-1.32, P<0.001) and CoV (1.30 [1.12-1.50], P<0.001) were associated with END. The association between END and BPV parameters differs according to renal function in minor ischemic stroke; BPV was associated with END in patients with renal impairment, but less in those with normal renal function.

Accuracy of diagnosing acute kidney injury by assessing urine output within the first week of life in extremely preterm infants.

Neonatal acute kidney injury (AKI) is associated with increased mortality and is often assessed with the neonatal modified Kidney Disease: improving Global Outcomes (KDIGO) classification, which uses changes in serum creatinine levels. However, because this classification has many drawbacks, a novel method, the neonatal Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (nRIFLE) classification for diagnosing neonatal AKI according to urine output (UO), was recently proposed. To date, no data on the incidence of AKI according to nRIFLE are available for extremely preterm infants (born at gestational age less than 28weeks). This study was conducted to clarify the association between incidence of AKI and in-hospital mortality in extremely preterm infants. Of 171 extremely preterm infants hospitalized from 2006 to 2020, 84 in whom indwelling bladder catheters were placed for UO measurements within 24h of life were included. The incidence of AKI was assessed using the nRIFLE classification. In-hospital mortality was compared between patients with AKI and those without it. The incidence of AKI during the first week of life was 56% and that of in-hospital mortality was significantly higher in patients with AKI (25.5%) than in those without it (2.8%). The odds ratio was 12.3 with 95% confidence interval ranging from 1.5 to 100.0. The incidence of AKI according to nRIFLE was higher than reported in most previous studies using the neonatal modified KDIGO classification, suggesting that assessment by nRIFLE criteria using UO may improve diagnostic accuracy of AKI in extremely preterm infants.

Characteristics of outpatients referred for a first consultation with a nephrologist: impact of different guidelines.

Chronic kidney disease (CKD) affects > 10% of the population but not all CKD patients require referral to a nephrologist. Various recommendations for referral to nephrologists are proposed worldwide. We examined the profile of Frenchpatients consulting a nephrologist for the first time and compared these characteristics with the recommendations of the International Kidney Disease: Improving Global Outcomes (KDIGO), the French "Haute Autorité de Santé" (HAS), and the Canadian Kidney Failure Risk Equation (KFRE). University Hospital electronic medical records were used to study patients referred for consultation with a nephrologist for the first time from 2016 to 2018. Patient characteristics (age, sex, diabetic status, estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (PCR), etiology reported by the nephrologist) and 1-year patient follow-up were analyzed and compared with the KDIGO, HAS and Canadian-KFRE recommendations for referral to a nephrologist.The stages were defined according to the KDIGO classification, based upon kidney function and proteinuria. RESULTS: The 1,547 included patients had a median age of 71 [61-79]years with 56% males and 37% withdiabetes. The main nephropathies were vascular (40%) and glomerular (20%). The KDIGO classification revealed 30%, 47%, 19%, 4% stages G1-2 to G5, and 50%, 22%, 28% stages A1-A3, respectively. According to KDIGO, HAS and KFRE scores, nephrologist referral was indicatedfor 42%, 57% and 80% of patients respectively, with poor agreement between recommendations. Furthermore, we observed 890 (57%) patients with an eGFR> 30ml/min and a urine protein to creatinine ratio0.5g/g, mostly aged over 65years (67%); 40% werediabetic,and 57% had aeGFR > 45ml/min/1.73m2, 56% were diagnosed asvascular nephropathy and 11% with unknown nephropathy. These results underline the importance of better identifyingpatients for referral to a nephrologist and informing general practitioners. Other referral criteria (age and etiology of the nephropathy) are debatable.

Association of Oliguria With Acute Kidney Injury Diagnosis, Severity Assessment, and Mortality Among Patients With Critical Illness

The current definition and staging of acute kidney injury (AKI) considers alterations in serum creatinine (sCr) level and urinary output (UO). However, the relevance of oliguria-based criteria is disputed. To determine the contribution of oliguria, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, to AKI diagnosis, severity assessment, and short- and long-term outcomes. This cohort study included adult patients admitted to a multidisciplinary intensive care unit from January 1, 2010, to June 15, 2020. Patients receiving long-term dialysis and those who declined consent were excluded. Daily sCr level and hourly UO measurements along with sociodemographic characteristics and severity scores were extracted from electronic medical records. Long-term mortality was assessed by cross-referencing the database with the Swiss national death registry. The onset and severity of AKI according to the KDIGO classification was determined using UO and sCr criteria separately, and their agreement was assessed. Using a multivariable model accounting for baseline characteristics, severity scores, and sCr stages, the association of UO criteria with 90-day mortality was evaluated. Sensitivity analyses were conducted to assess how missing sCr, body weight, and UO values, as well as different sCr baseline definitions and imputations methods, would affect the main results. Among the 15 620 patients included in the study (10 330 men [66.1%] with a median age of 65 [IQR, 53-75] years, a median Simplified Acute Physiology Score II score of 40.0 [IQR, 30.0-53.0], and a median follow-up of 67.0 [IQR, 34.0-100.0] months), 12 143 (77.7%) fulfilled AKI criteria. Serum creatinine and UO criteria had poor agreement on AKI diagnosis and staging (Cohen weighted κ, 0.36; 95% CI, 0.35-0.37; P < .001). Compared with the isolated use of sCr criteria, consideration of UO criteria enabled identification of AKI in 5630 patients (36.0%). Those patients had a higher 90-day mortality than patients without AKI (724 of 5608 [12.9%] vs 288 of 3462 [8.3%]; P < .001). On multivariable analysis accounting for sCr stage, comorbidities, and illness severity, UO stages 2 and 3 were associated with a higher 90-day mortality (odds ratios, 2.4 [95% CI, 1.6-3.8; P < .001] and 6.2 [95% CI, 3.7-10.5; P < .001], respectively). These results remained significant in all sensitivity analyses. The findings of this cohort study suggest that oliguria lasting more than 12 hours (KDIGO stage 2 or 3) has major AKI diagnostic implications and is associated with outcomes irrespective of sCr elevations.

Association of Preoperative Prognostic Nutritional Index and Postoperative Acute Kidney Injury in Patients with Colorectal Cancer Surgery.

The prognostic nutritional index (PNI) has been reported to be associated with postoperative complications and prognosis in cancer surgery. However, few studies have evaluated the association between preoperative PNI and postoperative acute kidney injury (AKI) in colorectal cancer patients. This study evaluated association of preoperative PNI and postoperative AKI in patients who underwent colorectal cancer surgery. This study retrospectively analyzed 3543 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into four groups by the quartile of PNI: Q1 (≤43.79), Q2 (43.79–47.79), Q3 (47.79–51.62), and Q4 (≥51.62). Multivariate regression analysis was performed to assess the risk factors for AKI and 1-year mortality. AKI was defined according to Kidney Disease Improving Global Outcomes classification (KDIGO) criteria. Additionally, we assessed surgical outcomes such as hospital stay, ICU admission, and postoperative complications. The incidence of postoperative AKI tended to increase in the Q1 group (13.4%, 9.2%, 9.4%, 8.8%). In the multivariate analysis, high preoperative PNI was significantly associated with low risk of postoperative AKI (adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93–0.99, p = 0.003) and low 1-year mortality (OR: 0.92, 95% CI: 0.86–0.98, p = 0.011). Male sex, body mass index, diabetes mellitus, and hypertension were risk factors for AKI. The Q1 (≤43.79) group had poor surgical outcomes, such as postoperative AKI (OR: 1.52, 95% CI: 1.18–1.95, p = 0.001), higher rates of ICU admission (OR: 3.13, 95% CI: 1.82–5.39, p < 0.001) and higher overall mortality (OR: 3.81, 95% CI: 1.86–7.79, p < 0.001). In conclusion, low preoperative PNI levels, especially in the Q1 (≤43.79), were significantly associated with postoperative AKI and surgical outcomes, such as hospital stay, postoperative ICU admission, and mortality.

Pediatric problems of stratification of the severity of stages, cardiovascular complications and renal forecast of chronic kidney disease by NKF-K / DOQI (2002) and KDIGO (2012) classifications

Chronic kidney disease (CKD) in children is a global problem worldwide. The article discusses the problem of stratification of CKD severity according to the classifications of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K / DOQI) (2002) and Kidney Disease Improving Global Outcomes (KDIGO) (2012) in pediatric patients. There are limitations in assessing severity of CKD stages C1-5 according to NKF-K / DOQI (2002) and KDIGO (2012) in children under 2 years of age who have a low glomerular filtration rate in contrast to adults. The stratification of the severity of stages 1-5 of CKD, cardiovascular complications and renal prognosis in children and adolescents according to the classifications NKF-K / DOQI (2002) [3] and KDIGO (2012) [14] are discussed. In adult patients with CKD, there is a compelling case for identifying of C3a and C3b sub stages in 3 stages of CKD according to KDIGO (2012) was that renal and cardiovascular prognosis are different with GFR 45-59 ml/min/1.73 m 2and GFR 30-44 ml/min/1.73 m 2 . The prognosis of the risk of developing cardiovascular diseases and complications for stages C2-5 in accordance with the KDIGO classification (2012) in children and adults differ. As follows from the publications, children with CKD in the pre-dialysis stages C2-4 form a high-risk group, with C4-5 on dialysis a group of very high risk of complications associated with cardiovascular pathology. Cardiovascular complications account for more than 30 % of all deaths of pediatric patients with CKD C4-5 on dialysis. The arguments justifying the allocation of CKD stages C1-5 in children under 2 years of age in accordance with the classification of NKF-K/DOQI (2002) are presented.

Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review.

IntroductionThe Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines recommend classifying patients by glomerular filtration rate (GFR) and albuminuria to predict chronic kidney disease (CKD) prognosis. The aim of this systematic review was to explore the epidemiological burden of CKD stratified by the KDIGO 2012 categories.MethodsMEDLINE® and Embase were searched for observational studies of patients with CKD with results stratified according to the KDIGO 2012 classification. Investigated outcomes were prevalence, incidence, and risk factors and complications of CKD, including mortality.ResultsThe review included ten observational studies with 3033 to 46,949 participants, conducted in the USA, China, France, Italy and Spain. The most frequently reported outcome was the prevalence of CKD (GFR categories G3–5), ranging from 2% to 17%. Most participants were normoalbuminuric, with 0.4–3.2% macroalbuminuric, and most fell within the KDIGO 2012 low-risk or moderate-risk groups, with 0.9–5.6% in the high-risk and 0.3–4.8% in the very high-risk groups. Although scarce, data on the prevalence of comorbidities in CKD according to the KDIGO classification suggest that they increase with albuminuria severity.ConclusionsPatients with CKD frequently have complications, but only a small proportion have severely increased albuminuria or fall within the KDIGO high-risk or very high-risk groups. These groups, however, are associated with the highest burden of disease, as comorbidities are more prevalent with increasing albuminuria severity. New studies framed by the KDIGO 2012 classification are needed to address key gaps in the understanding of CKD burden and outcomes.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01568-8) contains supplementary material, which is available to authorized users.

Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial.

In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin. Patients with type 2 diabetes, established atherosclerotic cardiovascular disease, and eGFR≥30 ml/min per 1.73 m2 at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. Post hoc, we analyzed cardiovascular and kidney outcomes, and safety, using the two-dimensional KDIGO classification framework. Of 6952 patients with baseline eGFR and urinary albumin-creatinine ratio values, 47%, 29%, 15%, and 8% were classified into low, moderately increased, high, and very high KDIGO risk categories, respectively. Empagliflozin showed consistent risk reductions across KDIGO categories for cardiovascular outcomes (P values for treatment by subgroup interactions ranged from 0.26 to 0.85) and kidney outcomes (P values for treatment by subgroup interactions ranged from 0.16 to 0.60). In all KDIGO risk categories, placebo and empagliflozin had similar adverse event rates, the notable exception being genital infection events, which were more common with empagliflozin for each category. The observed effects of empagliflozin versus placebo on cardiovascular and kidney outcomes were consistent across the KDIGO risk categories, indicating that the effect of treatment benefit of empagliflozin was unaffected by baseline CKD status. EMPA-REG OUTCOME, NCT01131676.

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program

Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio. Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m2 to treatment with canagliflozin or placebo. Canagliflozin or matching placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes. Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (Ptrend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greaterwithin higher KDIGO risk categories (Ptrend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (Ptrend= 0.04). Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m2. Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin. This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.

Acute Kidney Injury in SARS-CoV-2 Infected Critically Ill Patients

Objective: The main objective of this study is to evaluate the frequency of acute kidney injury (AKI) in COVID-19 infected patients who are hospitalized in the intensive care unit (ICU). Materials and Methods: This study was performed retrospectively on patients above 18 years of age who had a positive polymerase chain reaction (PCR), a typical chest computed tomography (CT) for COVID-19 disease. The patients were hospitalized in the medical ICU and kidney disease improving global outcomes (KDIGO) criteria was used for AKI classification. Results: We included 16 patients. The median age was 75 years and 88% were male. The most common co-morbid diseases were hypertension (HT) (56%) and cardiovascular disease (CVD) (44%). The median acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were 26 (19-32) and 7 (4-9) respectively. Patients median serum blood urea nitrogen (BUN) and creatinine levels were 27.8 (19.2-44.7) mg/dL, 1.32 (0.97-2.81) mg/dL respectively. According to the KDIGO classification: there was no AKI in 25% of the patients while, 19% stage 1, 12% stage 2 and 44% stage 3 AKI was observed. AKI developed in 75% of the patients. Conclusion: In this study we detected a high frequency of AKI in SARS-CoV2 infected patients hospitalized in the ICU.

Longitudinal Changes in Kidney Function Estimated from Cystatin C and Its Association with Mortality in Elderly Women

Background/Aims: Prospective data on age-related changes in kidney function are required, especially since the current Kidney Disease Improving Global Outcomes (KDIGO) definition has been suggested to classify a large number of elderly people with CKD. Objective: This study, a complement to our previous Cr-based study in the same cohort, is aimed at evaluating cystatin C (cysC)-based changes in kidney function during aging in older women and analyzing the association between CKD and mortality through 10 years of follow-up. Methods: cysC was available in 981 women from the Osteoporosis Prospective Risk Assessment (OPRA) cohort, all aged 75 years on entry. Reinvestigations were made after 5 (n = 685) and 10 years (n = 365). Kidney function was estimated (estimated glomerular filtration rate [eGFR]) using Chronic Kidney Disease Epidemiology Collaboration cysC and Caucasian, Asian, Pediatric, and Adult cysC equations and the change in function calculated. Women were staged equivalent to CKD stage 1, 2, 3a, or 3b–5 according to the KDIGO classification. Mortality risk was estimated for 5-year or 10-year follow-up time using Cox proportional hazard analyses (reference category, CKD stages 1 and 2). Results: Mortality risk for women with the worst kidney function (CKD stages 3b–5) increased during both 5-year follow-up times compared to that for women in stages 1 and 2 (age 75–80 years: adjusted Hazard Ratio [HR_adj] 3.9, 95% confidence interval [CI] 2.3–6.5; age 80–85 years: HR_adj 1.7, 95% CI 1.0–2.7). In contrast, women in stage 3a had increased risk only in the first 5-year follow-up (HR_adj 1.7, 95% CI 1.0–3.0, age 75–80 years). Change in kidney function amounted to a loss of 1.9 (±1.4) mL/min/1.73 m² per year during the 10-year follow-up, and at age 85 years, 4 of every 5 women had an eGFR equivalent to CKD. Conclusion: In the future, an age-adapted definition of CKD, lowering the threshold for CKD in the elderly, may be beneficial to avoid overdiagnosis of CKD.

Physicians’ Recognition and Management of Kidney Disease: A Randomized Vignette Study Evaluating the Impact of the KDIGO 2012 CKD Classification System

Rationale & ObjectiveThe Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification systems published in 2002 and 2012, respectively, are recommended worldwide and based on strong epidemiologic data. However, their impact on CKD recognition and management is not well evaluated in clinical practice, and we therefore investigated whether they help physicians recognize and appropriately care for patients with CKD.Study DesignRandomized vignette experiment with fractional factorial design based on 6 kidney-related scenarios and 3 laboratory presentation methods reflecting the CKD guidelines. Participants evaluated 1 of 3 subsets of the 18 vignettes (ie, 6 vignettes each with 4 answer alternatives).Setting & Participants249 interns, general practitioners, and residents/fellows attending postgraduate meetings and courses in Norway and the United States.InterventionKidney-related results (serum creatinine level and urinary albumin excretion) were presented as the “minimal data” (high/low levels), KDOQI-2002 (estimated glomerular filtration rate [eGFR] reported automatically), or KDIGO-2012 (eGFR + albuminuria categorization + risk for complications) laboratory report.OutcomeCKD management choice by physicians.ResultsWhen kidney laboratory data were presented as the KDOQI-2002 report (automatic eGFR calculation), there was a significantly higher odds for correct patient management decisions compared with the minimal data report (OR, 1.57; P < 0.001). Additional significant improvement was obtained with the KDIGO-2012 report (OR, 2.28 for correct answer vs minimal data report [P < 0.001]; OR, 1.45 compared to KDOQI-2002 report [P = 0.005]). The KDIGO classification system improved physician management in 4 of the 6 clinical scenarios covering a wide range of kidney-related topics. Interaction analysis showed that general practitioners and those with 1 to 3 years of internal medicine experience had the greatest improvements with the new presentation techniques.LimitationsPhysicians’ management was evaluated by theoretical scenarios rather than direct patient care.ConclusionsAutomatic GFR estimation, albuminuria categorization, and notification of the associated risk for complications improve most physicians` recognition and management of a wide range of CKD clinical scenarios.

The spectrum of kidney biopsy findings in HIV-infected patients in the modern era

HIV-associated kidney disease is evolving rapidly. Few North American studies have addressed modern trends and none has applied the 2018 Kidney Disease Improving Global Outcomes (KDIGO) pathologic classification. Therefore we performed a retrospective clinical-pathologic analysis of all HIV-positive patients with kidney biopsy interpreted at Columbia University from 2010-2018 using the KDIGO classification. The biopsy cohort of 437 HIV-positive patients had median age 53 years, including 66% males, 80% on anti-retroviral therapy, 57% with hypertension, 31% with diabetes, 27% with hepatitis C and 6% with hepatitis B co-infections. Race, known in 308 patients, included 58% black, 25% white and 17% Hispanic. Pathologic diagnoses were surprisingly diverse. Immune complex glomerulonephritis (ICGN) and diabetic nephropathy each outnumbered HIV-associated nephropathy, followed by tenofovir nephrotoxicity, FSGS- not otherwise specified (NOS) and global sclerosis (NOS). HIV-associated nephropathy was the most common disease in patients not on anti-retroviral therapy, and 94% were black. The association of FSGS (NOS) with black race (68%) and anti-retroviral therapy use (77%) suggests some cases may represent attenuated HIV-associated nephropathy. The most common ICGNs were IgA nephropathy and membranous glomerulopathy, both associating with anti-retroviral therapy (over 90%), followed by hepatitis C-associated proliferative ICGN. Among the 16 cases of uncharacterized ICGN lacking identifiable etiology, 69% were not on anti-retroviral therapy, possibly representing true HIV-associated immune complex kidney disease. Dual diseases occurred in 17% of patients, underscoring lesion complexity. Thus, anti-retroviral therapy has shifted the landscape of HIV-associated kidney disease toward diverse ICGN, diabetic nephropathy, and non-collapsing glomerulosclerosis, but has not eradicated HIV-associated nephropathy.

Proteinuria impacts patient survival differentially based on clinical setting: A retrospective cross-sectional analysis of cohorts from a single health system: Retrospective cohort study.

BackgroundChronic kidney disease (CKD) staging is improved by adding proteinuria to glomerular filtration rate (GFR). While proteinuria independently predicts CKD progression and mortality, the clinical setting of proteinuria determination has not been well-studied previously. The objective of our study is to determine whether clinical setting differentially impacts survival outcomes.MethodsKaplan-Meier and Cox proportional hazards analyses of overall survival were performed retrospectively for cohorts of outpatients (n = 22,918), emergency patients (n = 16,861), and inpatients (n = 12,304) subjected to urinalysis (UA) at a single health system in 2010. GFR (G1-G5) and proteinuria (A1:<30 mg, A2:30–300 mg, A3:>300 mg) were classified under Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.ResultsGFR and proteinuria levels varied more in inpatients than in emergency and outpatients. For each clinical population, survival significantly decreased with increasing proteinuria (A1>A2>A3, p < 0.05 for each comparison). The effect of proteinuria on survival differed by clinical setting, with statistical differences in all categories other than A3 in outpatients and emergency patients (p = 0.98). The strongest predictors of mortality were cancer diagnosis (HR: 3.07, p < 0.0001) and very-high KDIGO classification (HR: 2.01, p < 0.0001). Limitations include the retrospective observational study design and single health system analysis.ConclusionsThe value of UA to screen for proteinuria in each clinical setting is evident, but the impact of A2 and A3 level proteinuria on survival varies depending on the clinical scenario in which the determination was made. The clinical setting of proteinuria measurement should be factored into both patient care and clinical research activities.