Management of patients with diabetes and CKD: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Perkovic, Vlado; Agarwal, Rajiv; Fioretto, Paola; Hemmelgarn, Brenda R.; Levin, Adeera; Thomas, Merlin C.; Wanner, Christoph; Kasiske, Bertram L.; Wheeler, David C.; Groop, Per Henrik; Bakris, George L.; Cooper, Mark E.; Chae, Dong Wan; Davidson, Michael; Boer, Ian H. de; Zeeuw, Dick de; Fornoni, Alessia; Gnudi, Luigi; Herzog, Charles A.; Hung, Adriana M.; Jafar, Tazeen H.; Jardine, Meg; Jha, Vivekanand; Ji, Linong; Kahn, Steven E.; Langham, Robyn G; Lerma, Edgar V.; Ma, Rong; Makino, Hírofumi; Marre, Michel; Mauer, Michael; Metsärinne, Kaj; Nelson, Robert G.; Pécoits-Filho, Roberto; Pollock, Carol; Rajapurkar, Mohan; Rossing, Peter; Rychlík, Ivan; Sharma, Kumar; Stanton, Robert C.; Tesař, Vladimı́r; Tikkanen, Ilkka; Tomson, Charles; Toto, Robert D.; Tsukamoto, Yusuke; Tuttle, Katherine R.; Wada, Takashi; Williams, Winfred W.; Zhang, Hong; Zoungas, Sophia

doi:10.1016/j.kint.2016.09.010

Cited by 109 publications

(67 citation statements)

References 98 publications

(97 reference statements)

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“…incretins) together with basal long-acting insulin would be the safest in the case of HD. [18] The addition of MF would need to be carefully studied, if considered.…”

Section: Cmementioning

confidence: 99%

“…incretins) together with basal long-acting insulin would be the safest in the case of HD. [18] The addition of MF would need to be carefully studied, if considered.Also to be noted in the treatment of diabetes is the development of a novel, potentially life-saving, antidiabetic class of drug, the sodiumglucose cotransporter-2 (SGLT-2) inhibitors.[19] These drugs block the proximal tubular reabsorption of glucose, leading to glycosuria. It also results in increased sodium loss.…”

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confidence: 99%

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Recent important strategies in the management of chronic kidney disease

Meyers

Davies

2017

S Afr Med J

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The burden of chronic kidney disease (CKD) is considerably higher in low-and middle-income countries, which are less able than the developed world to cope with treating advanced renal failure owing to financial constraints. Prevention, early diagnosis and implementation of existing knowledge can improve outcomes. This review presents several recent advances to assist with avoiding and slowing down CKD progression and reducing common comorbid complications. The following are discussed: the possible use of metformin in patients with type 2 diabetes-related CKD; recent inexpensive important developments in the treatment of autosomal-dominant polycystic kidney disease; prevention of acidosis and the early dietary reduction of red meat consumption; and the therapeutic lowering of uric acid in persistent hyperuricaemia. Finally, an active and monitored exercise programme should be undertaken whenever possible. All of these recommendations have been shown to significantly slow the progression of CKD and increase cardiovascular protection. CME 731September 2017, Vol. 107, No. 9 CME addition to the multiple cardiovascular and renal complications of DM, renal dysfunction in the elderly is further compounded by the slow but progressive fall in glomerular filtration rate (GFR) in persons >45 years of age (i.e. ±1 mL/min/year) and also because people live longer. For many years the US Food and Drug Administration (FDA), the Regulatory Cooperation Council (RCC) in Canada and other regulatory bodies have indicated that the use of MF is contraindicated in patients with mild and moderate CKD (stages 3a and 3b) owing to the rarely reported but life-threatening complication of lactic acidosis (LA) (serum lactate levels ≥15 mmol/L).That LA does not occur in patients who receive MF, with an estimated GFR (eGFR) of 50 -30 mL/min., has been indicated in studies conducted by Inzucchi et al. [13] They showed that MF can be safely used in these patients, provided that certain guidelines are always followed. A Coch rane meta-analysis conducted on 47 096 patients with a follow-up of 86 067 patient-years compared the incidence of LA in patients who received MF with those who did not, irrespective of the eGFR.[14] They found that for the upper limit of 95% confidence the true incidence of LA was 6.3/100 000 patient-years for the MF group and 7.8/100 000 patient-years for the non-MF group.It is important to remember that before prescribing MF for any degree of renal function, certain rules are essential and must be fully adhered to. As many practitioners are either unaware or uncertain of the predisposing conditions, these are set out in Table 4.Mechanisms of MF-associated LA are not well elucidated, but include conversion of glucose to lactate in the splanchnic bed and inhibition of hepatic gluconeogenesis (i.e. from lactate, pyruvate and adenine). [15,16] It is essential that any patient with the abovementioned precipi ta ting disorders is instructed to immediately but temporarily withdraw the use of MF and present to a doctor. Patients h...

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“…incretins) together with basal long-acting insulin would be the safest in the case of HD. [18] The addition of MF would need to be carefully studied, if considered.…”

Section: Cmementioning

confidence: 99%

mentioning

confidence: 99%

Recent important strategies in the management of chronic kidney disease

Meyers

Davies

2017

S Afr Med J

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“…Current strategies for delaying progression of DKD are based around risk factor reduction—primarily blood sugar and blood pressure control—and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker therapy 6, 7. It has been decades since a new class of medicines was introduced to delay disease progression.…”

Section: Introductionmentioning

confidence: 99%

New clinical trial designs for establishing drug efficacy and safety in a precision medicine era

Heerspink

List

Perkovic

2018

Diabetes Obesity Metabolism

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Despite advances in pharmacotherapy, diabetic kidney disease (DKD) remains associated with a high burden of micro‐ and macrovascular complications often leading to premature mortality. New therapies are highly desirable to mitigate the burden of this disease. However, there are a number of barriers that hamper drug development in DKD. These include, amongst others, the lengthy and complex clinical trials required to prove drug efficacy and safety, inefficiencies in clinical trial conduct, and the high costs associated with these development programs. In this review a number of aspects are discussed, aiming to identify opportunities to transform and innovate drug development for DKD. Many clinical trials in DKD, as well as in other areas, face difficulties in timely and efficient enrolment of participants. To address this issue a network of sites should be created that are continuously recruiting individuals with DKD and collecting crucial information that can be used to understand prognosis and prognostic factors, and more importantly to serve as a pool of participants for recruitment to randomized trials. Second, the current clinical endpoints are late events in the progression of DKD. Endpoints based on lesser declines in estimated glomerular filtration rate (eGFR) or changes in albuminuria can shorten follow‐up and/or lead to smaller and cheaper trials. Enrichment by enrolling clinical trial populations based on biomarker profiles is another approach that may facilitate clinical trial efficiency and conduct. Biomarkers can be used to individualize treatment by targeting populations more likely to respond leading to smaller and more efficient trials. Finally, using new trial design such as basket, umbrella or more broadly platform trials to assess a number of therapies simultaneously offers the potential to transform the drug development process in DKD. There are a number of opportunities to transform development approaches for new therapies for DKD. Platform trials along with appropriate biomarker‐based enrichment strategies offer the possibility to foster drug development in a precision medicine era.

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“…However, the management of diabetes in this population is challenging owing to a variety of reasons that include the following: the high variability of blood glucose, a predisposition to asymptomatic hypoglycemia, altered pharmacokinetics of several glucose-lowering medications, but most importantly, the fact that glycated hemoglobin A1c (HbA1c) is a less accurate indicator of glycemic state [5, 6]. On this basis, international guidelines mention the potential role of alternative glycemic markers among diabetic patients with chronic kidney disease (CKD), but call for stronger clinical evidence that will elucidate their applicability to people with specific stages of CKD [6-8]. …”

Section: Introductionmentioning

confidence: 99%

Comparison of Glycemic Markers in Chronic Hemodialysis Using Continuous Glucose Monitoring

et al. 2017

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Background: Glycated hemoglobin A1c (HbA1c) among diabetic hemodialysis patients continues to be the standard of care, although its limitations are well recognized. This study evaluated glycated albumin (GA) and glycated serum protein (GSP) as alternatives to HbA1c in detecting glycemic control among diabetic hemodialysis patients using continuous-glucose-monitoring (CGM)-derived glucose as reference standard. Methods: A CGM system (iPRO) was applied for 7 days in 37 diabetic hemodialysis patients to determine glycemic control. The accuracy of GA and GSP versus HbA1c in detecting a 7-day average glucose ≥184 mg/dL was evaluated via receiver-operating-characteristic (ROC) analysis. Results: CGM-derived glucose exhibited strong correlation (r = 0.970, p < 0.001) and acceptable agreement with corresponding capillary glucose measurements obtained by the patients themselves in 1,169 time-points over the 7-day-long CGM. The area under ROC curve (AUC) for GA, GSP, and HbA1c to detect poor glycemic control was 0.976 (0.862–1.000), 0.682 (0.502–0.862), and 0.776 (0.629–0.923) respectively. GA levels >20.3% had 90.9% sensitivity and 96.1% specificity in detecting a 7-day average glucose ≥184 mg/dL. The AUC for GA was significantly higher than the AUC for GSP (difference between areas: 0.294, p < 0.001) and the AUC for HbA1c (difference between areas: 0.199, p < 0.01). Conclusion: Among diabetic hemodialysis patients, GA is a stronger indicator of poor glycemic control assessed with 7-day-long CGM when compared to GSP and HbA1c.

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Management of patients with diabetes and CKD: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Cited by 109 publications

References 98 publications

Recent important strategies in the management of chronic kidney disease

Recent important strategies in the management of chronic kidney disease

New clinical trial designs for establishing drug efficacy and safety in a precision medicine era

Comparison of Glycemic Markers in Chronic Hemodialysis Using Continuous Glucose Monitoring

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