COVID-19 and kidneys

COVID-19 poses a real threat to patients with comorbid conditions such as diabetes mellitus (DM), hypertension, cardiovascular, renal or hepatic disorders. Kidney damage is very likely in people with diabetes who have undergone a new infection, and the risk of developing acute renal injury is associated with mortality. Potential mechanisms of kidney involvement in the clinical picture of the disease may include cytokine damage, cross-organ damage, and systemic effects that determine the treatment strategy. These mechanisms are closely interrelated and are important for individuals on extracorporeal therapy and kidney transplants. Autopsy data provide evidence of SARS-CoV-2 virus invasion into kidney tissue with damage to tubular epithelium cells and podocytes, and red blood cell aggregation in severely COVID-19 patients. By including individuals with chronic kidney disease in planned COVID-19 research protocols, an evidence base for effective and safe treatments can be generated

Chronic kidney disease in patients with type 2 diabetes: new targets of medicine action

Diabetes mellitus type 2 (DM2) is socially important disease, becoming non-infectious epidemic due to increasing prevalence. Chronic kidney disease (CKD) is one of the most common diabetic complications. Kidney injury signs and/or estimated glomerular filtration rate (eGFR) decrease are seen in 40-50% of patients with DM2. Three groups of factors are considered to be the basis of CKD development and progression in DM2: metabolic, hemodynamic, inflammation and fibrosis. Existing drugs that are used in patients with CKD and DM2 first of all target hemodynamic and metabolic disturbances, but their action against inflammation and fibrosis is indirect. Hyperactivation of mineralocorticoid receptors (MR) is considered as one of the main trigger factors of end-organ damage in patients with DM2 due to inflammation and fibrosis. Development of selective nonsteroidal MR antagonists (MRA) as a new class of medications is directed to demonstrate positive effects from blocking this pathophysiological pathway of CKD development and overcome the steroidal MRAs’ shortcomings. Hence pathophysiological hyperactivation of MR with subsequent inflammation and fibrosis in patients with CKD in DM2 is considered a promising therapeutic target for the new drugs with cardionephroprotective effect

A simultaneous pancreas-kidney transplantation for type 1 diabetes mellitus after a long-term of receiving hemodialysis renal replacement therapy. Clinical сase

At the present time, a simultaneous pancreas-kidney transplantation (SPKT) is an effective method of treatment for patients on renal replacement therapy by hemodialysis program in the outcome of the terminal stage of diabetic nephropathy. This method of treatment solves several problems: it reduces the severity of intoxication syndrome, contributes to the achievement of euglycemia in most cases, which certainly allows to slow the progression of micro- and macrovascular complications of diabetes. Despite of positive effect of euglycaemia and kidney function normalization, the accumulated metabolic memory legacy of long-term uncompensated diabetes mellitus is realized, which makes a posttransplantational rehabilitation of patients difficult. A duration of hemodialysis therapy is known as a cardiovascular events risk factor, which affects the surgery result and favorable posttransplant period. More often after successful SPKT microvascular diabetic complications are stabilized, but macrovascular diabetic complications, diabetic neuroosteoarthropathy and mineral and bone disease are progressed. That’s why is necessary to perform regular examination after SPKT by a team of specialists, including nephrologist, endocrinologist, cardiologist, ophthalmologist with correction of ongoing therapy. Therefore both the preparation of  the patient for transplantation with the earliest possible placement on the waiting list and the post-transplant rehabilitation afterwards are extremely important

Simultaneous pancreas‐kidney transplantation in type 1 diabetes mellitus. Clinical options

Simultaneous pancreas-kidney transplantation (SPKT) is the most promising treatment option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) due to diabetic nephropathy (DN). Successful SPKT eliminates uremic intoxication and hyperglycemia – the leading trigger of vascular diabetic complications. Therefore, euglycemia is an important metabolic change in patients after surgery and remains only one of the factors for the saved renal allograft functioning. In the case of resuming renal replacement therapy by dialysis after SPKT, the management and monitoring of the pancreatic graft remains open. Special attention to the pancreatic graft’s function is due to both the potential risk of surgical complications, and some probability of T1DM relapse with the need to resume insulin therapy. In patients with saved function of both transplants, the assessment of the dynamics of diabetic complications in general becomes more important. The results of few studies in this regard remain contradictory. Thus, clinical options can be unpredictably diverse and require not only search for the root cause, but also optimization of rehabilitation tactics, even if the expected results are achieved

The structure of mineral and bone disorders in patients with сhronic kidney disease of the 5th dialysis stage, taking into account the presence or absence of a diagnosis of type 1 diabetes mellitus

BACKGROUND: In patients with end-stage CKD, receiving renal replacement therapy (RRT) with programmed hemodialysis (HD), the severity of complications is associated with metabolic disturbances: accumulation of uremic toxins, nephrogenic anemia, secondary hyperparathyroidism (SHPT), extraskeletal calcification, impaired clearance and rhythm of hormone secretion.AIM: To evaluate the main biochemical and hormonal parameters, and manifestations of mineral bone disease (MBD) in patients receiving RRT with HD, before and after hemodialysis, taking into account the presence or absence of diabetes mellitus.MATERIALS AND METHODS: We divided all patients receiving RRT with HD in two groups: #1 (n=24) — patients with DM, #2 (n=16) — patients without DM. All of them had their blood analyzed before and immediately after the HD. Data analysis was performed with the Statistica 13 (StatSoft, USA). A prognostically significant model was considered at p<0.05.RESULTS: The level of iPTH, both at baseline and after HD, was lower in group #1 (p<0.001). The level of alkaline phosphatase (AP) was significantly higher in group #2 (p=0.012). In both groups before HD, a high incidence of hypocalcemia was detected (according to albumin-corrected calcium in group #1 in 58.3%, in group #2 in 43.7% of cases, p = 0.366) and hyperphosphatemia (in 66.7% and in 43 .7% of cases, respectively, p=0.151). Hypocalcemia after HD in group #1 persisted in 14%, in group #2 — in 20% of cases (p>0.05); hyperphosphatemia in group #1 was completely leveled, in group #2 it persisted in 7% of cases (p=0.417). Prior to the HD session, group #1 had significantly higher levels of RAGE, glucagon, immunoreactive insulin (IRI), cortisol, and glucose than after the HD session (p<0.05). In group #2, after HD, the levels of glucagon, IRI and cortisol significantly decreased (p<0.05), and the level of 3-nitrotyrosine (3-HT) increased significantly (p=0.026). In group #1, fibrocalcinosis of the heart valves according to ECHO and calcification of the arteries of the lower extremities according to ultrasonic doplerography were more common than in group #2 (42% vs 25%, p<0.001 and 75% vs 37.5%, p=0.018, respectively). (χ2)). Compression fractures occurred with the same frequency in both groups (60%). A decrease in bone mineral density (BMD) to the level of osteopenia was noted more often in group #1 (50% vs 18.8%), and osteoporosis was more common in group #2 (68.8% vs 33.3%) (p<0.001, χ2).CONCLUSION: The low level of PTH in group #1 may reflect the effect of diabetes on calcium-phosphorus metabolism. Patients with DM have an increased risk of renal osteodystrophy with a low bone turnover because of a number of metabolic factors inherent in diabetes. At the same time, the dynamics of phosphorus and calcium indicators during the HD procedure were similar

The advisory board resolution on the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes

Type 2 diabetes is characterized by increasing incidence and prevalence all-over the world. Current therapeutic management of type 2 diabetes is complex and is based not only on glycemic control, but also on cardiovascular and renal risks reduction. In previous years the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) increased in Russian Federation. Some manufacturers of the most widely used GLP-1 RA reported the supply decline in several countries. On Advisory board with participation of the Russian Endocrinology Association members the topics of SGLT2i and GLP-1 RA use in type 2 diabetes were discussed. The experts made conclusion that the decrease in access to GLP-1 RA does not pose serious risk for treatment of type 2 diabetes patients. SGLT2i show benefits in risk reduction of HF and CKD progression compering to GLP-1 RA, and in general show comparable efficacy in risk reduction of ACVD outcomes.  SGLT2i show less glycemic efficacy in comparison with GLP-1 RA, and their replacement may need adding antidiabetic agents from other groups

Сhronic kidney disease complications in patients with type 1 diabetes mellitus after simultaneous pancreas-kidney transplantation – potential role of oxidative stress and glycation end products

BACKGROUND: Normoglycaemia in patients with diabetes mellitus type 1 (T1DM) after simultaneous pancreas-kidney transplantation (SPKT) is very interesting in regards to chronic kidney disease (CKD) complications dynamics depending of posttransplantation period and possible targets of potential treatment from the point of view “metabolic memory” AIM: To evaluate the relationship between oxidative stress indicators and advanced glycation end products and complications of end-stage renal disease (ESRD) in patients with T1DM аnd a long-term history of diabetes decompensation, who reached stable euglycemia after SPKT. MATERIALS AND METHODS: The study included 20 patients with compensation of carbohydrate metabolism after SPKT performed from November 2011 to September 2018. Assessment included examination of complications of ESRD (arterial hypertension, dyslipidemia, anemia, mineral and bone disorder) and analysis of "metabolic memory" markers: 3-nitrothyrosine (3-NT), superoxide dismutase (SOD), advanced glycation end products (AGE) and AGE receptor (RAGE). We performed follow-up examination of patients included in the early postoperative period (1st day/week) in 6-12 months after SPKT. RESULTS: All patients with DM1 duration for 22 [19; 28] years, diabetic nephropathy (DN) 8 [6; 14] years and duration of renal replacement therapy (dialysis) for 3 [1.5; 4] years reached euglycemia (HbA1c 5,5 [5,1; 5,8] %; С-peptide 3,2 [2,45; 3,63] ng/ml) after 6 month of surgical treatment. Despite of stable graft function (estimated glomerular filtration rate (eGFR) CKD-EPI 84 [69; 95] ml/min/1.73m2) 35% of patients still needed antihypertensive therapy, 40% needed treatment with recombinant human erythropoietin (RHuEPO) and 15% – ferrotherapy. With vitamin D deficiency, observed in 80% of cases (13.3 [9.3; 18.5] ng/ml), 55% of patients had secondary hyperparathyroidism, 45% – osteoporosis. The results of the correlation analysis revealed the association of the state of ESRD target organs with the studied "metabolic memory" markers: oxidative stress and AGE-RAGE system. CONCLUSIONS: SPKT as the way to achieve compensation of carbohydrate metabolism and uremia does not provide regress of diabetes and complications of ESRD. Analysis of "metabolic memory" markers indicate their direct contribution to the persistence of metabolic consequences of diabetic nephropathy (DN). Found trends need more long-lasting observation and enlargement of study groups

Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

Inhibitors of the sodium-glucose cotransporter type 2 (SGLT2i) are a modern class of antihyperglycemic drugs with an insulin-independent mechanism of action. Due to its ability to effectively lower blood glucose levels, improve a number of other cardiometabolic parameters (body weight, blood pressure, uric acid), as well as reduce cardiovascular and renal risks, SGLT2i have become drugs of choice for many of patients with type 2 diabetes mellitus (T2DM). Meanwhile, along with the generally recognized classes-effects of this group of drugs, there are intragroup features, including those associated with their different selectivity in sodium-glucose cotransporters of types 1 and 2 (SGLT1 and SGLT 2). For example, one of the most studied SGLT2i, canagliflozin, in addition to its inhibitory activity against SGLT2, can also moderately block SGLT1 in the intestine and kidneys that could give a maximum efficiency in the control glycemia and others cardiometabolic parameters. In addition, canagliflozin improves not only cardiovascular, but also renal prognosis in patients with T2DM, which is reflected in the corresponding indications in the summary of product characteristics of the drug. This document summarize the established and new data regarding the efficacy and safety of canagliflozin, as well as its place in the treatment of T2DM

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease

Aim: present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points. Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion. Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients