Kidney Disease: Improving Global Outcomes Guidelines Research Articles

Analysis of the short-term prognosis and risk factors of elderly acute kidney injury patients in different KDIGO diagnostic windows

Background and aimsFollow-up observation was performed on elderly acute kidney injury (AKI) patients to analyze the short-term prognosis and risk factors of AKI patients in the 48-h diagnostic window and 7-day diagnostic window of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.MethodsInpatients aged ≥ 75 years in the geriatric ward of the People’s Liberation Army General Hospital, China, between January 2007 and December 2015 were selected as the research subjects. According to two diagnostic criteria in the KDIGO guidelines, patients were divided into a 48-h diagnostic window group and a 7-day diagnostic window group. The medical data of the patients were divided into the death group and the survival group for analysis based on the survival condition of the patients after 90 days of AKI. Factors that affected the 90-day survival of patients in the 48-h diagnostic window and 7-day diagnostic window groups were analyzed using multivariate Cox regression.ResultsDuring the follow-up period, a total of 652 patients were enrolled in this study. Among them, 623 cases were men, accounting for 95.6% of the patients. The median age was 87 (84–91) years. According to the KDIGO staging criteria, there were 308 (47.2%) cases in AKI stage 1, 164 (25.2%) cases in stage 2, and 180 (27.6%) cases in stage 3. Among the 652 patients, 334 (51.2%) were diagnosed with AKI based on the 48-h diagnostic criteria window, and 318 (48.8%) were diagnosed with AKI based on the baseline 7-day diagnostic criteria. The 90-day mortality of AKI patients was 42.5% in the 48-h diagnostic window and 24.2% in the 7-day diagnostic window. The multivariate Cox analysis results showed that low mean arterial pressure (HR = 0.966; P < 0.001), low serum prealbumin level (HR = 0.932; P < 0.001), infection (HR = 1.448; P = 0.047), mechanical ventilation (HR = 1.485; P = 0.038), high blood urea nitrogen (BUN) level (HR = 1.026; P < 0.001), blood magnesium level (HR = 2.560; P = 0.024), and more severe AKI stage (stage 2: HR = 3.482; P < 0.001 and stage 3: HR = 6.267; P < 0.001) were independent risk factors affecting the 90-day mortality of elderly patients in the 48-h diagnostic window, whereas low body mass index (HR = 0.851; P < 0.001), low mean arterial pressure (HR = 0.980; P = 0.036), low serum prealbumin level (HR = 0.950; P = 0.048), low serum albumin level (HR = 0.936; P = 0.015), high BUN level (HR = 1.046; P < 0.001), and more severe AKI stage (stage 2: HR = 4.249; P = 0.001 and stage 3: HR = 9.230; P < 0.001) were independent risk factors affecting the 90-day mortality of elderly patients in the 7-day diagnostic window.ConclusionsThe clinical differences of AKI and risk factors for 90-day mortality in elderly AKI individuals vary depending on the definition used. An increment of Scr ≥ 26.5 μmol/L in 48 h (48-h KDIGO window) alone predicts adverse clinical outcomes.

MON-308 MANAGEMENT OF HENOCH-SCHONLEIN PURPURA NEPHRITIS IN AUSTRALIA AND NEW ZEALAND: DOES IT DIFFER FROM KIDNEY DISEASE IMPROVING GLOBAL OUTCOMES GUIDELINES?

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, with renal involvement occurring in 40-60% of paediatric patients within 4 to 6 weeks of the initial presentation. Majority of paediatric patients with HSP nephritis (HSPN) have mild disease, however a small proportion of patients present with renal impairment, nephrotic syndrome, or both. Kidney Disease Improving Global Outcomes (KDIGO) guidelines assist with management of different severities of HSPN but with low level of evidence. We aimed to evaluate the variance in current practice in management of paediatric HSPN by paediatric nephrologists in Australia and New Zealand. We designed an electronic survey consisting of various clinical scenarios of different severities in paediatric patients with HSPN. All of the questions were in multiple-choice format; majority allowing for participants to provide multiple management choices if required. The link to the survey was e-mailed to all members (trainees and consultants) of the Australian and New Zealand Paediatric Nephrology Association (ANZPNA). Survey was sent to 55 members of ANZPA. The responses were collated and analysed. The response rate was 30%, majority of the respondents being Staff Specialists of more than 10 years of experience. Majority of the respondents would commence treatment for mild HSPN with angiotensin converting enzyme inhibitors (ACEi), which is consistent with KDIGO guideline. Prednisolone was added in conjunction with ACEi for HSPN International Study of Kidney Diseases in Children (ISKDC) classification II and above. More complex HSPN including macroscopic haematuria and nephrotic-range proteinuria highlighted variability in practice amongst the ANZPNA group. For ISDKC classification IIIb and more, a non-steroid based immunosuppressive therapy was added to other therapies, but there was no consistency in treatment of choice. Rapidly progressive glomerulonephritis (RPGN) scenario was usually treated with IV methylprednisolone and cyclophosphamide with occasional use of plasma exchange. The majority of Australia and New Zealand Paediatric Nephrologists follow the KDIGO recommendations for treatment of mild HSPN. There is a wide variation in practice for moderate-to-severe HSPN with no consistency in choice of non-steroid immunosuppression, based on clinical presentation or histological findings except for RPGN. The wide variation in clinical practice highlights the lack of current evidence-based recommendations for HSPN treatment.

Clinical practice guidelines for the provision of renal service in Hong Kong: Potential Kidney Transplant Recipient Wait-listing and Evaluation, Deceased Kidney Donor Evaluation, and Kidney Transplant Postoperative Care.

Clinical practice guidelines for the provision of renal service in Hong Kong: Potential Kidney Transplant Recipient Wait-listing and Evaluation, Deceased Kidney Donor Evaluation, and Kidney Transplant Postoperative Care.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Adherence to Kidney Disease: Improving Global Outcomes Mineral and Bone Guidelines for Monitoring Biochemical Parameters

Background: Mineral and bone disorder (MBD) is common in patients with chronic kidney disease (CKD), and is associated with risk of fractures, cardiovascular disease, and death. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend monitoring CKD-MBD biochemical markers, including parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D (25D), calcium, and alkaline phosphatase (ALP), in patients with moderate-to-severe CKD. Methods: To determine guideline adherence, we used administrative claims records from the 20% sample of Medicare beneficiaries with Parts A, B, and D coverage, 2007 to 2015, and identified cohorts of patients with nondialysis stage 3, 4, or 5 CKD. Testing for biochemical markers during follow-up was defined based on laboratory procedure codes. Baseline factors associated with laboratory testing were determined using logistic regression. All analyses were performed separately by CKD stage. Results: A total of 640,946 stage 3, 136,278 stage 4, and 22,076 stage 5 CKD patients, 50.2–52.9% women, mean age 74.4–78.0 years, were followed for a mean of 2.5, 1.3, and 0.7 years respectively. The frequency of testing was low for PTH (35.2–48.2%), phosphorus (46.6–62.0%), and 25D (29.3–46.7%). Testing was somewhat higher for calcium (88.1–95.4%) and ALP (63.5–88.1%); most tests were features of larger panels (e.g., basic metabolic panel). Older age, most comorbid conditions, and lack of prior nephrology care were associated with lower likelihood of testing. Conclusions: In fee-for-service Medicare beneficiaries, laboratory testing for CKD-MBD biochemical markers appears to be suboptimal in relation to KDIGO guidelines. Competing priories, such as management of comorbid disease and preparation for renal replacement therapy, may distract from CKD-MBD monitoring.

ACUTE KIDNEY INJURY IS INDEPENDENTLY ASSOCIATED WITH ALL-CAUSE MORTALITY FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION

THE AIM.To determine clinical value of acute kidney injury (AKI) in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) for mortality along postransplant period.PATIENTS ANDMETHODS.Ninety hematopoietic stem cell transplantat (HSCT) recipients (46 males, 44 females) were enrolled in the observational prospective study. Clinical and laboratory data were monitored and assessed 7 days prior to HSCT (week 0), on the posttransplant weeks 1, 2, 3, 4 and 5. AKI was diagnosed according to KDIGO (Kidney Disease Improving Global Outcomes) guidelines. All-cause mortality was registered along 1 year of posttransplant period. AKI associations with death risk were estimated in cumulative survival analysis and Cox multivariate regression models adjusted for other confounders.RESULTS.AKI was diagnosed in 67 (74%) out of 90 patients. The majority of patients (84%) suffered from AKI 1 stage (KDIGO). AKI 2+3 stage (KDIGO) was found in 16% of patients. Renal replacement therapy was used in 4 (6%) patients with AKI. Cumulative survival rate following HSCT reached 75%. 28 deaths (31%) were registered within 1 year following HSCT. AKI was associated with lower cumulative survival following HSCT. AKI was independently associated with the risk of death according to multivariate Cox regression analyses adjusted for other confounders.CONCLUSION. AKI may be considered as a significant clinical predictor of unfavorable allogeneic HSCT outcome, taking into account its independent association with increased risk of posttransplant all-cause mortality.

Guidelines and clinical practice at the primary level of healthcare in patients with type 2 diabetes mellitus with and without kidney disease in five European countries.

The number of patients with type 2 diabetes mellitus and diabetes mellitus-associated chronic kidney disease varies considerably between countries. Next to differences in genetic as well as life style risk factors, varying practices in medical care delivery might cause this diversity. The PROVALID study recruited 4000 patients with type 2 diabetes mellitus at the primary level of healthcare in five European countries (Austria, Hungary, The Netherlands, Poland and Scotland). Baseline data were used to describe patient characteristics and compare the adherence to ADA (American Diabetes Association) and KDIGO (Kidney Disease: Improving Global Outcomes) guidelines with respect to metabolic and blood pressure control, use of renin-angiotensin system-blocking agents, statins and acetylsalicylic acid between the countries. About 34.8% of the population had evidence of diabetes mellitus-associated chronic kidney disease. The median HbA1c level of the cohort was 6.8% (ranging from 6.5 in Poland to 7.0% in Scotland). Mean blood pressure was 136/79 (±17/10) and significantly higher in subjects with elevated albuminuria. These individuals also were more often treated with renin-angiotensin system-blocking agents (74.1% vs 84.6%), whereas the use of statins was driven by cardiovascular comorbidity. Acetylsalicylic acid was used in only 28.9% subjects. Despite similar cardiovascular comorbidities and renal function, the use of renin-angiotensin system-blocking agents varied significantly between the countries from 66.7% to 87.4%. An even higher variability was observed for patients >40 years of age using statins (39.8%-82.7%) and administration of acetylsalicylic acid in patients older than 50 years (5.2%-43.8%). Our study shows that medical practice in type 2 diabetes mellitus patients with and without renal disease is different in European countries. Longitudinal follow-up will reveal if this diversity affects clinical endpoints.

Vitamin D, bone alkaline phosphatase and parathyroid hormone in healthy subjects and haemodialysed patients from West Africa: impact of reference ranges and parathyroid hormone generation assays on the KDIGO guidelines.

BackgroundThe Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend targets based on multiples of the upper limit of normal (ULN) of parathyroid hormone (PTH) concentration. However, the ULN has not always been correctly established by manufacturers. While it is known that the ULN is supposed to be higher in African Americans than in Caucasians, it is largely unknown in Africans.MethodsWe established the ULN of PTH concentration in a population of 240 healthy Ivorians using second- and third-generation PTH assays before and after supplementation with 100 000 IU of cholecalferol. We measured the levels of PTH, bone alkaline phosphatase, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in 100 haemodialysed Ivorian patients.ResultsThe prevalence of vitamin D deficiency in Ivory Coast is low. The ULN obtained using the third-generation PTH assay was similar to that obtained in Caucasians but was higher when PTH was measured using the second-generation PTH assay. According to the KDIGO guidelines, ∼20% of the haemodialysed patients were below twice the ULN and 30% were above nine times the ULN. Approximately 25% of the patients were even >12 times the ULN. We observed a discrepancy in the results between the two PTH assays (14%) that was relatively more important than what we observed from previous studies in Caucasians using the same strategy.ConclusionsWe found a low prevalence of vitamin D deficiency in a tropical country like Ivory Coast. We also established the PTH reference range, which could prove useful for the follow-up of haemodialysed patients, particularly for the large number of patients suffering from secondary hyperparathyroidism who are at high risk of adverse bone events.

Prevalence of Chronic Kidney Disease and Poor Diagnostic Accuracy of Dipstick Proteinuria in Human Immunodeficiency Virus-Infected Individuals: A Multicenter Study in Japan.

BackgroundChronic kidney disease (CKD) has become one of the common comorbid conditions affecting the human immunodeficiency virus (HIV) population. Human immunodeficiency virus-infected individuals are at increased risk of developing CKD, and they are likely to experience faster progression of renal dysfunction compared with HIV-uninfected individuals. Albuminuria represents not only kidney damage but also manifests metabolic syndrome and vascular dysfunction.MethodsWe conducted a multicenter, cross-sectional study involving 2135 HIV-infected individuals in Japan to test the prevalence of CKD and proteinuria/albuminuria. Urine sample was analyzed by both dipstick test and albumin-to-creatinine ratio (ACR) assay. Chronic kidney disease was classified according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The diagnostic performance of dipstick test to detect albuminuria (ACR ≥30 mg/g) was evaluated.ResultsThe prevalence of CKD, evaluated by K/DOQI and KDIGO guidelines, was 15.8% and 20.4%, respectively. Age, total cholesterol level, prevalence of hypertension, diabetes mellitus, and hepatitis C infection tended to increase, whereas levels of hemoglobin, serum albumin, and CD4 cell count tended to decrease as CKD risk grades progressed. Proteinuria and albuminuria were present in 8.9% and 14.5% of individuals, respectively. Dipstick test ≥1+ to detect albuminuria had an overall sensitivity of 44.9% and specificity of 97.2%.ConclusionsThe KDIGO guideline may enable physicians to capture HIV-infected patients at increased risk more effectively. The sensitivity of dipstick proteinuria to detect albuminuria is so poor that it may not serve as an alternative in HIV-infected individuals.

Chronic kidney disease in type 2 diabetes mellitus patients: Comparison of KDIGO and KDOQI guidelines

BackgroundChronic kidney disease (CKD), has become a public health concern as it has been reported to cause adverse outcomes such as kidney failure and premature death. This cross sectional study compared the Kidney Disease: Improving Global Outcomes (KDIGO) and Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines in assessing the prevalence of CKD in Type 2 diabetes Mellitus (T2DM) patients. MethodsWe consecutively sampled a cross-section of 202 T2DM patients from the Ho municipality in the Volta region (Ghana). Structured pre-tested questionnaires were administered to obtain information on gender, age, body mass index (BMI), systolic and diastolic blood pressure, medication used, duration on medication, and duration of diabetes. Serum creatinine and urine protein were estimated using standard protocols and CKD was classified according to KDIGO and KDOQI guidelines. ResultsThe prevalence of CKD was 63.4% and 58.4% using the KDIGO and KDOQI guidelines respectively. The prevalence of mildly decreased renal function or worse (eGFR < 60/ml/min/1.73 m2) was 10.4% for KDIGO guideline and 7.9% for KDOQI guidelines with an excellent agreement between both definitions showing bias = −0.129, 95%CI = (−0.17 to −0.08) on Bland-Altman analysis. Participants older than 70 years were more likely to have CKD when KDIGO criteria was used (P = 0.018). The prevalence of albuminuria was 47.0% with 21.9% presenting with 1+ and 2+ grades. ConclusionKDIGO guideline estimates higher prevalence of CKD than KDOQI guidelines in the same study population. KDIGO guideline might help in early detection and proper classification of CKD which will illicit stage-specific treatment.

Association between intensity of statin therapy and mortality in persons with chronic kidney disease.

The 2013 American College of Cardiology/American Heart Association lipid guideline recommends statin dosing based on intensity, rather than targeting specific low-density lipoprotein cholesterol (LDL-C) concentrations, among general populations. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) lipid guideline recommends statins for most adults with chronic kidney disease (CKD), but dose-dependent statin effects in CKD are unclear. We performed a retrospective cohort study of US veterans with CKD Stages G3a, G3b or G4, and new, persistent statin use, from 2005 to 2015. We tested the association of intensity of statin therapy [categorized as low (expected LDL-C reduction <30%), medium (30 to <50%) or high (≥50%)] during the initial 1-year exposure period, with all-cause mortality over the subsequent 4 years. We used Cox proportional hazard models to evaluate the association between statin intensity and all-cause mortality, adjusting for demographics, comorbidities and laboratory measurements. Our cohort included 65 292 persons, of whom 40 124 (61.5%) had CKD G3a, 20 183 (30.9%) G3b and 4985 (7.6%) G4. Overall, 4878 (7.5%) used high-intensity, 39 070 (59.8%) used moderate-intensity and 21 344 (32.7%) used low-intensity statins. High-intensity statins were used more in recent years, and among persons diagnosed with atherosclerotic cardiovascular disease. There was no association between statin intensity and mortality in unadjusted or multivariable-adjusted analyses. There were no significant associations between statin intensity over 1 year of exposure and subsequent mortality among US veterans with CKD. This supports the current KDIGO guideline recommendations to use statins and dosages that have been studied specifically in CKD populations, rather than intensity-based dosing.

The KDIGO acute kidney injury guidelines for cardiac surgery patients in critical care: a validation study

BackgroundThe Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI) guidelines assign the same stage of AKI to patients whether they fulfil urine output criteria, serum creatinine criteria or both criteria for that stage. This study explores the validity of the KDIGO guidelines as a tool to stratify the risk of adverse outcomes in cardiac surgery patients.MethodsProspective data from consecutive adult patients admitted to the cardiac intensive care unit (CICU) following cardiac surgery between January 2013 and May 2015 were analysed. Patients were assigned to groups based on the criteria they met for each stage of AKI according to the KDIGO guidelines. Short and mid-term outcomes were compared between these groups.ResultsA total of 2267 patients were included with 772 meeting criteria for AKI-1 and 222 meeting criteria for AKI-2. After multivariable adjustment, patients meeting both urine output and creatinine criteria for AKI-1 were more likely to experience prolonged CICU stay (OR 4.9, 95%CI 3.3–7.4, p < 0.01) and more likely to require renal replacement therapy (OR 10.5, 95%CI 5.5–21.9, p < 0.01) than those meeting only the AKI-1 urine output criterion. Patients meeting both urine output and creatinine criteria for AKI-1 were at an increased risk of mid-term mortality compared to those diagnosed with AKI-1 by urine output alone (HR 2.8, 95%CI 1.6–4.8, p < 0.01). Patients meeting both urine output and creatinine criteria for AKI-2 were more likely to experience prolonged CICU stay (OR 16.0, 95%CI 3.2–292.0, p < 0.01) or require RRT (OR 11.0, 95%CI 4.2–30.9, p < 0.01) than those meeting only the urine output criterion. Patients meeting both urine output and creatinine criteria for AKI-2 were at a significantly increased risk of mid-term mortality compared to those diagnosed with AKI-2 by urine output alone (HR 3.6, 95%CI 1.4–9.3, p < 0.01).ConclusionsPatients diagnosed with the same stage of AKI by different KDIGO criteria following cardiac surgery have significantly different short and mid-term outcomes. The KDIGO criteria need to be revisited before they can be used to stratify reliably the severity of AKI in cardiac surgery patients. The utility of the criteria also needs to be explored in other settings.

Estimating Time to ESRD in Children With CKD

The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. Observational cohort study. Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD-derived "bedside" equation. Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk. Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models. Observational study, used cross-validation rather than external validation. CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

Renal Replacement Therapy in Acute Kidney Injury - Indication and Implementation

Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with a worse short- and long-term outcome. The KDIGO (Kidney Disease: Improving Global Outcomes) guidelines suggest to implement preventive strategies in high-risk patients. Definition and classification of acute kidney injury according to the KDIGO criteria are based on an increase in serum creatinine and/or a decrease in urinary output. Renal replacement therapy (RRT) is the only supportive measure in patients with severe AKI. The KDIGO guidelines recommend to initiate RRT immediately if an absolute indication exists. However, in the absence of absolute indication, there are no recommendations when to start RRT in AKI patients with a progressive decline of renal function. Continuous or intermittent techniques of renal replacement therapy may be used equally for treatment of acute kidney injury. In hemodynamically instable patients and patients with increased intracranial pressures continuous renal replacement therapy is recommended. Although weak evidence exists, regional citrate anticoagulation is suggested for patients receiving continuous renal replacement therapy and systemic heparin anticoagulation is suggested for patients receiving intermittent renal replacement therapy. The KDIGO guidelines recommend to deliver an effluent volume of 20 - 25 ml/kg/h for CRRT in AKI.

Assessment of Glomerular Filtration Rate and End-Stage Kidney Disease Risk in Living Kidney Donor Candidates: A Paradigm for Evaluation, Selection, and Counseling.

Living donor kidney transplantation is the preferred treatment option for ESRD. However, recent data suggest a small increase in the long-term risk of kidney failure in living kidney donors when compared to healthy nondonors. These data have led to a need for reconsideration of how donor candidates are evaluated and selected for donation. A Kidney Disease: Improving Global Outcomes (KDIGO) work group completed a comprehensive clinical practice guideline for evaluation of living kidney donor candidates in 2017, based on systematic evidence review, de novo evidence generation, and expert opinion. Central to the evaluation framework is assessment of glomerular filtration rate (GFR), which is used to screen for kidney disease and aid the prediction of long-term kidney failure risk after donation. Accurate estimation of the level of GFR and risk of kidney failure, and communication of estimated risks, can support evidence-based donor selection and shared decision-making. In this review, we discuss approaches to optimal GFR estimation in the donor evaluation process, long-term risk projection, and risk communication to donor candidates, integrating recommendations from the new KDIGO guideline, other recent literature, and experience from our own research and practice. We conclude by highlighting topics for further research in this important area of transplant medicine.

HMOX1 and Acute Kidney Injury in Sickle Cell Anemia

▪Acute kidney injury (AKI) is associated with tubulointerstitial fibrosis and nephron loss and may lead to an increased risk for subsequently developing chronic kidney disease (CKD). In adults with sickle cell anemia (SCA), high rates of CKD have been consistently observed, although the incidence and risk factors for AKI are less clear.We evaluated the incidence of AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a rise in serum creatinine by ≥0.3mg/dL within 48 hours or ≥1.5 times baseline within seven days, in 158 of 299 adult SCA patients enrolled in a longitudinal cohort from the University of Illinois at Chicago. These patients were selected based on the availability of genotyping for α-thalassemia, BCL11A rs1427407, APOL1 G1/G2, and the HMOX1 rs743811 and GT-repeat variants. Median values and interquartile range (IQR) are provided. With a median follow up time of 66 months (IQR, 51-74 months), 137 AKI events were observed in 63 (40%) SCA patients. AKI was most commonly observed in the following settings: acute chest syndrome (25%), an uncomplicated vaso-occlusive crisis (VOC)(24%), a VOC with pre-renal azotemia determined by a fractional excretion of sodium <1% or BUN-to-creatinine ratio >20:1 (14%), or a VOC with increased hemolysis, defined as an increase in serum LDH or indirect bilirubin level >1.5 times over the baseline value at the time of enrollment (12%).Compared to individuals who did not develop AKI, SCA adults who developed an AKI event were older (AKI: median and IQR age of 35 (26-46) years, no AKI: 28 (23 - 26) years; P=0.01) and had a lower estimated glomerular filtration rate (eGFR) (AKI: median and IQR eGFR of 123 (88-150) mL/min/1.73m2, no AKI: 141 (118-154) mL/min/1.73m2; P=0.02) by the Kruskal-Wallis test at the time of enrollment.We evaluated the association of a panel of candidate gene variants with the risk of developing an AKI event. These included loci related to the degree of hemolysis (α-thalassemia, BCL11A rs1427407), to chronic kidney disease (APOL1 G1/G2 risk variants), and to heme metabolism (HMOX1) . Using a logistic regression model that adjusted for age and eGFR at the time of enrollment, the risk of an AKI event was associated with older age (10-year OR 2.6, 95%CI 1.4-4.8, P=0.002), HMOX1 rs743811 (OR 3.1, 95%CI 1.1-8.7, P=0.03), and long HMOX1 GT-repeats, defined as >25 repeats (OR 2.5, 95%CI 1.01-6.1, P=0.04).Next, we assessed whether AKI is associated with a more rapid decline in eGFR and with CKD progression, defined as a 50% reduction in eGFR, on longitudinal follow up. Using a mixed effects model that adjusted for age and eGFR at the time of enrollment, the rate of eGFR decline was significantly greater in those with an AKI event (β = -0.51) vs. no AKI event (β = -0.16) (P=0.03). With a median follow up time of 66 months (IQR, 51-74 months), CKD progression was observed in 21% (13/61) of SCA patients with an AKI event versus 9% (8/88) without an AKI event. After adjusting for age and eGFR at the time of enrollment, the severity of an AKI event according to KDIGO guidelines (stage 1 if serum creatinine rises 1.5-1.9 times baseline, stage 2 if the rise is 2.0-2.9 times baseline, and stage 3 if the rise is ≥3 times baseline or ≥4.0 mg/dL or requires renal replacement therapy) was a risk factor for CKD progression (unadjusted HR 1.6, 95%CI 1.1-2.3, P=0.02; age- and eGFR-adjusted HR 1.6, 95%CI 1.1-2.5, P=0.03).In conclusion, AKI is commonly observed in adults with sickle cell anemia and is associated with increasing age and the HMOX1 GT-repeat and rs743811 polymorphisms. Furthermore, AKI may be associated with a steeper decline in kidney function and more severe AKI events may be a risk factor for subsequent CKD progression in SCA. Future studies understanding the mechanisms, consequences of AKI on long-term kidney function, and therapies to prevent AKI in SCA are warranted. DisclosuresGordeuk:Emmaus Life Sciences: Consultancy.

KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD)

Chronic kidney disease-mineral and bone disorder (CKD-MBD) encompasses laboratory and bone abnormalities and vascular calcification and has deleterious effects on clinical outcomes. KDOQI (Kidney Disease Outcomes Quality Initiative), an initiative of the National Kidney Foundation, addressed this issue with the publication of a clinical practice guideline for bone metabolism and disease in CKD in 2003, and 2 years later, a new definition and classification scheme for CKD-MBD was developed following a KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference. The initial KDIGO guideline on CKD-MBD was then published in 2009. New evidence was subsequently reviewed at the 2013 KDIGO Controversies Conference, andin 2017, KDIGO issued a clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD. This commentary presents the views of the KDOQI CKD-MBD work group convened bythe National Kidney Foundation. The KDOQI work group agrees with most of the KDIGO guideline update recommendations, particularly the suggestions regarding bone mineral density testing, joint assessments of longitudinal trends in mineral metabolism markers, and dietary phosphate counseling focused on phosphate additives. However, the KDOQI work group has some concerns about the suggestions related to hypocalcemia and hypercalcemia, phosphate-binder choice, and treatment of abnormal parathyroid hormone concentrations. The overall goal of this commentary is to provide a broad discussion for the US nephrology community regarding CKD-MBD and its diagnosis, prevention, and treatment.

Traitement de la glomérulonéphrite extramembraneuse

Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, evolving to 30 % end-stage renal disease after 10 years, in the absence of specific treatment. In 2009, the M-type phospholipase A2 receptor (PLA2R), a podocyte membrane glycoprotein, was identified as the first autoantigen involved in more than 70 % of primitive membranous nephropathy. Many studies have reported that high titers of PLA2R antibodies are correlated with a lower risk of spontaneous or immunosuppressant-induced remission, a higher risk of nephrotic syndrome and of progression to end-stage renal disease. Treatment is still challenging and controversial because of potential toxicity and lack of a reliable prognosis marker. In the past, the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines recommended immunosuppressive therapies as steroids and alkylating agents or cyclosporine in patients with persistent nephrotic syndrome or impaired renal function. Recent studies and one multicentric randomised controlled trial brought clear evidence to support the use of rituximab in these patients: rituximab regimen induces immunological and clinical remission in patients with membranous nephropathy, with a high safety profile. However, they have provided important data on the impact of PLA2R antibodies assessment as a prognostic biomarker in patients with membranous nephropathy. The next step will be the integration of this biomarker in KDIGO guidelines and the recommendation of rituximab as a first line immunosuppressive therapy in patient with persistent nephrotic syndrome due to membranous nephropathy.

“ALTERATIONS IN PARATHORMONE, CALCIUM AND PHOSPHORUS LEVELS IN CKD PATIENTS ON MAINTENANCE HAEMODIALYSIS IN A HOSPITAL SETTING IN PUNJAB.”

Objective: Many people who have severe chronic kidney disease (CKD) will eventually develop kidney failure and will require dialysis. The controlof parathormone (PTH), phosphorus, and calcium metabolism is one of the objectives in an adequate dialysis protocol. Therefore, we conductedthis study to describe alterations in PTH, calcium, and phosphorous homeostasis in patients with CKD on hemodialysis in our center. Our study alsoaimed to find an association between hormonal and biochemical abnormalities in CKD patients, who have been on hemodialysis for ≥5 months andcomparing the results obtained with that recommended by Kidney Disease Improving Global Outcomes (KDIGO) guidelines.Methods: This was a hospital-based cross-sectional observational study. The study population of 330 patients (&gt;18 years) on maintenancehemodialysis coming to dialysis Unit of Department of Medicine of Gian Sagar Hospital, Ramnagar (Patiala), over a period of 3 years (2012-2015),were enrolled in the study. Each patient was considered only once for the study. In addition, biochemical analysis of serum intact PTH (iPTH), correctedcalcium, phosphorus, total alkaline phosphatase (tALP), serum creatinine, blood urea, serum albumin, and hemoglobin of all cases was done usingfully automated equipment. All statistical analyses were performed using SPSS statistical software, version 17.Results: The study population of 330 patients comprised adults, mainly illiterate (54.5%) predominantly belonging to the rural (66.4%) strata witha mean age of 52.67±15.05 (range: 25-98 years). The abnormality in the laboratory profile of the patients was found to be hyperparathyroidism in40.3% as compared to hypoparathyroidism in 33.5% and normal iPTH levels in 26.2%. Hypocalcaemia was detected in 50.6% and hyperphosphatemiain 62.1% of the patients. There was statistically significant association of serum iPTH, with corrected calcium and phosphorus (P=0.032 and P=0.035,respectively). Corrected calcium was also significantly associated with phosphorus (P=0.001) and tALP (P=0.007).Conclusion: We showed in the present study that disorders of mineral metabolism are common in hemodialysis patients and that only a smallproportion adheres to the targets as advised in the KDIGO guidelines for bone metabolism and disease in CKD. We demonstrated that these disordersare associated with important negative clinical outcomes, such as increased all-cause lack survival, more muscle and bone problems. Our findings,therefore, support a strict control of mineral metabolism in dialysis patients. Further research and progress in this area are required to establish amore rational approach with a view toward improving patient outcomes.Keywords: Parathormone, Calcium, Phosphorus, Hemodialysis.

Why overestimate or underestimate chronic kidney disease when correct estimation is possible?

There is no doubt that the introduction of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 14 years ago, and their subsequent updates, have substantially contributed to the early detection of different stages of chronic kidney disease (CKD). Several recent studies from different parts of the world mention a CKD prevalence of 8-13%. However, some editorials and reviews have begun to describe the weaknesses of a substantial number of studies. Maremar (maladies rénales chroniques au Maroc) is a recently published prevalence study of CKD, hypertension, diabetes and obesity in a randomized, representative and high response rate (85%) sample of the adult population of Morocco that strictly applied the KDIGO guidelines. When adjusted to the actual adult population of Morocco (2015), a rather low prevalence of CKD (2.9%) was found. Several reasons for this low prevalence were identified; the tagine-like population pyramid of the Maremar population was a factor, but even more important were the confirmation of proteinuria found at first screening and the proof of chronicity of decreased estimated glomerular filtration rate (eGFR), eliminating false positive results. In addition, it was found that when an arbitrary single threshold of eGFR (<60 mL/min/1.73 m2) was used to classify CKD stages 3, 4 and 5, it lead to substantial 'overdiagnosis' (false positives) in the elderly (>55 years of age), particularly in those without proteinuria, haematuria or hypertension. It also resulted in a significant 'underdiagnosis' (false negatives) in younger individuals with an eGFR >60 mL/min/1.73 m2 and below the third percentile of their age-/gender-category. The use of the third percentile eGFR level as a cut-off, based on age-gender-specific reference values of eGFR, allows the detection of these false positives and negatives. There is an urgent need for additional quality studies of the prevalence of CKD using the recent KDIGO guidelines in the correct way, to avoid overestimation of the true disease state of CKD by ≥50% with potentially dramatic consequences.