Finerenone.

In developed countries, diabetes mellitus (DM) is one of the main causes of end stage renal disease (ESRD). In addition, the development of chronic kidney disease (CKD) further increases the already significantly increased cardiovascular (CV) risk in patients with diabetes. Both albuminuria and impaired renal function predict CV disease-related morbidity. The multifactorial pathogenesis of DM-related CKD involves structural, physiological, hemodynamic, and inflammatory processes. Instead of a so-called glucocentric approach, current evidence suggests that a multimodal, interdisciplinary treatment approach is needed to also prevent further progression of CKD and reduce the risk of cardiovascular events. Combined antihypertensive, antihyperglycemic and hypolipidemic therapy is the basis of a comprehensive approach to prevent the progression of diabetic kidney disease. According to recent evidence, adjunctive therapy with the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone - in addition to the use of an ACE (angiotensin converting enzyme) or AT1 (angiotensin II receptor subtype 1) blocker and an SGLT2 (sodium-glucose cotransporter-2) inhibitor - represents an effective therapeutic tool to improve nephroprotection in CKD. The aim of this review is to provide brief information on this promising pharmacotherapeutic approach to the treatment of diabetic kidney disease.

Differential diagnosis of back pain.

Back pain (BP) is among the most common reasons for seeking medical attention worldwide. The nature of BP depends on the causative stimulus and its anatomical location. Clinically, BP is manifested by pain, muscle tension, and stiffness. The development of BP is a very complex, multifactorial process in which not only somatic stimuli (anatomical structures), but also psychosocial effects are involved. Using a variety of criteria, BP can be divided into specific where the cause of pain is known, nonspecific wherein the cause remains unclear, or according to its duration (i.e., acute, subacute, and chronic back pain). Simple low back pain must be distinguished from inflammatory BP. Inflammatory BP is one of the symptoms of spondyloarthritides. It is typically a resting pain of insidious onset, peaking at night or in the morning associated with morning stiffness, improved with exercise, and responding to non-steroidal antirheumatic drugs. A red-flag system was developed for the early identification of at-risk patients with a potentially severe disease presenting with BP. Early diagnosis and identification of the cause of complaints often requires multidisciplinary cooperation. The treatment involves pharmacological agents (analgesic and muscle relaxation therapies) and nonpharmacological approaches (rehabilitation, surgical intervention, etc.).

The use of moxonidine in the treatment of arterial hypertension.

Moxonidine is an oral antihypertensive drug from the group of 2nd generation sympatholytics. In patients with mild to moderate hypertension, moxonidine lowers blood pressure (BP) as effectively as most first-line antihypertensives when used as monotherapy - if appropriate, and is also an effective adjunctive therapy in combination with other antihypertensives. It improves metabolic profile in patients with hypertension and diabetes mellitus or impaired glucose tolerance, is very well tolerated, has a low potential for drug interactions and is administered in a single daily dose. Thus, moxonidine is a good choice especially in the treatment of patients with more severe forms of hypertension, especially as adjunctive therapy in patients with metabolic syndrome or with mental stress.

Renal parenchymal hypertension: relevant new aspects.

Renal parenchymal disease is the most common cause of secondary hypertension, accounting for up to 5% cases of all cases of systemic hypertension. Renal parenchymal hypertension occurs as a complication of a wide variety of glomerular and tubulointerstitial diseases and may aggravate the decline of kidney function. The pathophysiology of renal parenchymal hypertension represents a combined interaction of the impaired sodium handling leading to volume expansion, alteration of the renin-angiotensin system, abnormalities in endogenous vasodepressor compounds and possibly enhanced activity of vasoactive substances. Renal parenchymal hypertension can occur in acute and chronic kidney disease, manifesting early in the renal function impairment. It often requires complex pharmacological treatment of blood pressure and is prognostically unfavorable in terms of cardiovascular and renal complications. This form of secondary hypertension can often be successfully treated by therapy of the underlying renal disease. In case of insufficient blood pressure compensation, renal impairment progresses. The aim of this paper is to give a brief overview of renoparenchymatous hypertension, current diagnostic possibilities and principles of therapy.

Proteinuria from an internists point of view.

A basal level of proteinuria is about 30-100 mg/day, the upper limit of basal proteinuria does not exceed 150 mg/day which is considered non-pathology. Albumin accounts approximately 15 % of basal protein in the urine, other plasma proteins (immunoglobulins, β-2 microglobulin, Tamm-Horsfall mucoprotein) comprise the remaining 85 % of total quantity non-pathology proteinuria. Persistent proteinuria present for more than three months already meets the definition of chronic kidney disease independently of the stage of the estimated glomerular filtration rate. Patients are classified as A1-A3 based on the level of albuminuria. Examination of the albumin in the urine is one of the single sensitive indicators of chronic kidney disease. Proteinuria is an independent risk factor for cardiovascular disease, overall mortality and end stage renal failure both in general population and in population with chronic kidney disease. Presence of the urinary protein is associated with a higher mortality rate in critically ill patients. The degree of proteinuria after kidney transplantation predicts graft and patient survival in this population. Pharmacological and non-pharmacological treatments that attenuate proteinuria have been associated with better prognosis of kidney disease.

Proteinuria from an internists point of view.

A basal level of proteinuria is about 30-100 mg/day, the upper limit of basal proteinuria does not exceed 150 mg/day which is considered non-pathology. Albumin accounts approximately 15 % of basal protein in the urine, other plasma proteins (immunoglobulins, β-2 microglobulin, Tamm-Horsfall mucoprotein) comprise the remaining 85 % of total quantity non-pathology proteinuria. Persistent proteinuria present for more than three months already meets the definition of chronic kidney disease independently of the stage of the estimated glomerular filtration rate. Patients are classified as A1-A3 based on the level of albuminuria. Examination of the albumin in the urine is one of the single sensitive indicators of chronic kidney disease. Proteinuria is an independent risk factor for cardiovascular disease, overall mortality and end stage renal failure both in general population and in population with chronic kidney disease. Presence of the urinary protein is associated with a higher mortality rate in critically ill patients. The degree of proteinuria after kidney transplantation predicts graft and patient survival in this population. Pharmacological and non-pharmacological treatments that attenuate proteinuria have been associated with better prognosis of kidney disease.

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis). Renal-biopsy specimens from 34 patients with IgAN and 7 patients with ANCA-associated vasculitis were used. In addition, we used 15 healthy portions of renal-tissue specimens from kidneys after nephrectomy for cancer as control specimens. Expression of TLR 4, 7, 8, and 9 was assessed using immunohistochemical staining of paraffin-embedded renal-biopsy tissue specimens with specific antibodies and evaluated semiquantitatively by light microscopy. Linear discriminant analysis (LDA) was used to test whether intrarenal staining of TLR 4, 7, 8, and 9 distinguished patients with IgAN from controls or correlated with eGFR and/or proteinuria. eGFR was calculated using the creatinine-based formula. Moreover, the biopsies from patients with IgAN were scored according to the Oxford Classification. LDA showed that staining for TLR 4, 7, 8, and 9 was more intense in specimens from IgAN patients compared to normal kidney tissues. The intensity of intrarenal staining of TLRs discriminated four groups of IgAN patients with different eGFR and proteinuria and MEST scoring.

[Gliflozins slow down the progression of diabetic kidney disease]. / Nové moznosti ovlivnení progrese diabetického onemocnení ledvin.

Until recently progression of diabetic kidney disease could have been slowed down only by the inhibition of the renin-angiotensin system. Inhibitors of SGLT2 (sodium-glucose transporter 2) in the proximal tubulus of the kidney induce natriuresis and by the activation of the tubuloglomerular feedback increase the tone of the afferent arteriole and decrease the glomerular pressure. Empagliflozin in the study EMPA-REG Outcome significantly decreased the risk of progression of diabetic kidney disease and further analyses also demonstrated its potent antiproteinuric effect. Taking into consideration the concomitant cardioprotective and renoprotective effect of empagliflozin and high mortality, cardiovascular morbidity and risk of progression into end-stage renal disease of diabetic kidney disease treatment with gliflozins should be considered in all patients with diabetic nephropathy. Exact place of gliflozins in the treatment of patients with diabetic kidney disease will be established by the further ongoing studies with other gliflozins with primary renal endpoints.Key words: diabetic kidney disease - empagliflozin - glomerular hypertension - progression.

Placental growth factor, pregnancy-associated plasma protein-A, soluble receptor for advanced glycation end products, extracellular newly identified receptor for receptor for advanced glycation end products binding protein and high mobility group box 1 levels in patients with acute kidney injury: a cross sectional study.

BACKGROUND: Placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products (sRAGE), extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD). However, their clinical significance in acute kidney injury (AKI) is unknown. The aim of this cross-sectional study was to determine whether selected biomarkers are changed in AKI patients. METHODS: Serum PlGF, PAPP-A, sRAGE, EN-RAGE and HMGB-1 levels were assessed in 40 patients with AKI, 42 CKD 5 patients, 31 haemodialysis patients (HD) and 39 age-matched healthy controls. RESULTS: PAPP-A was elevated in AKI (20.6 ± 16.9 mIU/L) compared with controls (9.1 ± 2.3 mIU/L, p < 0.001). PlGF was not increased in AKI (11.7 ± 7.4 pg/mL) versus controls (8.5 ± 2.4 pg/mL, n.s.), as well as sRAGE was not elevated in AKI (2400 ± 1400 pg/mL) compared with controls (1760 ± 730 pg/mL, n.s), but was lower compared with CKD 5 (3200 ± 1500 pg/mL, p < 0.05); EN-RAGE was elevated in AKI 480 ± 450 ng/mL in comparison with controls (60 ± 62 ng/mL), CKD 5 (190 ± 120 ng/mL), and HD (120 ± 100 ng/mL), all p < 0.001. Similarly, HMGB-1 was increased in AKI (5.8 ± 7.5 ng/mL) versus controls (1.7 ± 1.4 ng/mL), CKD 5 (3.2 ± 3.1 ng/mL) and HD (2.5 ± 2.1 ng/mL), all p < 0.001.In AKI group, in multivariate regression analysis: PAPP-A levels were associated with transferrin (p <0.001), negatively with albumin (p < 0.01) and prealbumin (p < 0.05); PlGF levels were associated with C--reactive protein (p < 0.001). EN-RAGE levels were associated with ferritin (p < 0.01) and orosomucoid (p = 0.02), and HMGB-1 levels with leukocyte count (p < 0.01) and negatively with proteinuria (p = 0.02). CONCLUSIONS: In AKI patients, PAPP-A, EN-RAGE and HMGB1 are elevated, but sRAGE and PlGF are not increased. Whereas PAPP-A correlates with markers of nutrition; PlGF, EN-RAGE and HMGB-1 are related to inflammatory parameters.