Multimorbidity in nephrotic syndrome.

Nephrotic syndrome (NS) is characterized by high proteinuria (over 3,5g/24 hrs), hypalbuminaemia, general edemas and hypercoagulation. Beside of primary glomerulonephritides this is found in secundary glomerulopaties eg. diabetes, systemic inflammatory diseases, oncology, damage by drugs and poisoning, by alergy, serious infections and in children from hereditary reasons. The most frequent reason for NS in adults patiens is diabetes and diabetes with nephropathy represents almost 40% of dialysed patiens. From this point of view, there is great interest focusing on gliflozins (SGLT2 inhibitors) with positive nephroprotecive effect. It leads do increasing of glycosuria with concomitant natriuresis and osmotic diuresis. The effect is proportional to glomerulal filtration, but the effect on natriuresis stay in all stages of renal insufficiency.

Preoperative assessment in older adults.

Advanced social care and higher level of medical intervention in elderly allow to prolong life expectancy in seniors, and therefore the number of elderly patients has risen rapidly in last decades. Management of elderly patients examination before surgery is routinely organized by general practitioners and internists with an aim to facilitate the surgery team work; to help anesthesiologists focus mainly on strategy of anesthesia (without any other special examination) and surgeons to realize/accomplish effective and save surgery, including elective surgery procedures. Key issue is to summarize the level of risk for surgery and compare it to prediction of follow-up with respect of mortality and morbidity as well as function status after surgery. Special attention should be focused on frailty seniors, all items together including quality of life and life expectancy should be carefully analyzed. Correctly prepared pre-operative report remarkable improves prognosis in high risk seniors.

Minimally invasive surgery and one-day care.

Due to population aging in developed countries, it has become necessary to prepare a functional health care plan for the elderly. One of the possibilities to improve postoperative outcomes and recovery in elderly patients is to perform common surgical procedures in the regime of one-day surgery. We compared elderly patients who underwent surgery in a large university hospital with elderly patients who underwent surgery in a facility dedicated to one-day surgery. The homogeneity and clinical outcomes of the two groups were statistically analyzed. Complications were assessed according to the Clavien-Dindo classification. There were no statistically significant differences in demographic data and pre-operative risk assessment (ASA). The one-day surgery group had fewer complications and a shorter average hospital stay. Advanced age is not the only criterion for assessing the biological state of the patient and therefore does not always necessitate surgical care in a university hospital setting with a high volume of acute and complicated cases. Many elderly patients will benefit from a more individualized approach and healthcare facilities that specialize solely in elective procedures. When indicating elderly patients for one-day surgery, their health status is more important than their calendar age.

Acute toxic kidney injury.

Substances toxic to the kidney are legion in the modern world. The sheer number and variety, their mutual interactions and, metabolism within the body are a challenge to research. Moreover, the kidney is especially prone to injury owing to its physiology. Acute kidney injury (AKI) induced by poisonous or primarily nephrotoxic substances, may be community acquired with ingestion or inhalation or nosocomial. Many nephrotoxic plants, animal poisons, medications, chemicals and illicit drugs can induce AKI by varying pathophysiological pathways. Moreover, the epidemiology of toxic AKI varies depending on country, regions within countries, socioeconomic status and health care facilities. In this review, we have selected nephrotoxic insults due to medication, plants, animal including snake venom toxicity, environmental, (agri)chemicals and also illicit drugs. We conclude with a section on diagnosis, clinical presentation and management of poisoning accompanied by various organ dysfunction and AKI.

Adherence to ketoacids/essential amino acids-supplemented low protein diets and new indications for patients with chronic kidney disease.

BACKGROUND: Low protein diets (LPD) have long been prescribed to chronic kidney disease patients with the goals of improving metabolic abnormalities and postpone the start of maintenance dialysis. METHODS: We reviewed the recent literature addressing low protein diets supplemented with ketoacids/essential aminoacids prescribed during chronic kidney disease and their effects on metabolic, nutritional and renal parameters since 2013. RESULTS: We show new information on how to improve adherence to these diets, on metabolic improvement and delay of the dialysis needs, and preliminary data in chronic kidney disease associated pregnancy. In addition, data on incremental dialysis have been reviewed, as well as potential strategies to reverse protein energy wasting in patients undergoing maintenance dialysis. CONCLUSION: These recent data help to better identify the use of low protein diets supplemented with ketoacids/essential aminoacids during chronic kidney disease.

[Suplemented restricted diet in old patients with chronic renal disease]. / Suplementované restriktivní diety u nemocných vyssího veku s chronickým onemocnením ledvin.

In last decades was confirmed remarkable increase in number of old patients with chronic kidney disease. Despide of developments in dialysis technology and kidney transplantation there is a growing number of old patients who are not suitable for these methods. Recently were published data showing long-term effect of protein restricted diet supplemented with keto amino acids in elderly. Based on our results obtained in re-analysis of 3 000 patients we can confirm also good compliance and low risk of malnutrition.Key words: chronic kidney disease - keto amino acids - old age - restricted diet.

Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 µmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx.

[Serum concentration and tubular resorption of sodium and chloride in patients with chronic renal disease]. / Sérové koncentrace sodíku a chloridu a tubulární resorpce techto iontu u pacientu s chronickým renálním onemocnením.

Tubular transport of sodium (TNa+) and chloride (TCl-) is decreased in patients with chronic kidney disease. The decrease of TCl- is relatively lower than that of TNa+. These changes of tubular transport of Na+ and Cl- participate on the development of acid base disturbance in patients with chronic kidney disease and with their glomerular filtration rate lower than 0.5 ml/s/1.73 m2.

Early exercise training after renal transplantation and asymmetric dimethylarginine: the effect of obesity.

BACKGROUND/AIMS: To assess, in a prospective cohort study of 238 renal transplant patients, our hypothesis that elevated ADMA levels may be influenced by physical exercise and obesity. METHODS: Blood samples before and after six months were obtained from 116 transplant patients participating in an aerobic exercise (Group I). A control group consisted of 122 matched transplant patients who did not exercise regularly (Group II). RESULTS: There were no significant differences in ADMA levels between both groups before the training program (Group IB vs. Group IIB). After six months of exercise, ADMA levels in Group I decreased (Group IB vs. Group IA : 3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; p< 0.01) and were lower compared to those in Group II (Group IA vs. Group IIA : 2 11 ± 0 23 vs 3 25 ± 0 34 µmol/L; p< 0 01) Analysis of our results in obese renal transplant recipients (BMI B 30 kg/m(2)) confirmed a smaller effect of exercise training (Group IBO vs Group IAO : 3 75 ± 0 52 vs 3 45 ± 0 45; p< 0 05 and Group IAO vs. Group IIAO : 3.45 ± 0.45 vs. 3.74 ± 0.62; p<0.05). Blood lipids, HbA1C, insulin, and systolic BP were also affected by the training program. CONCLUSION: Elevated ADMA levels were significantly decreased by early exercise after renal transplantation. The effect of exercise was smaller in obese patients.

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors.

It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution.

Use of phosphate-binding agents is associated with a lower risk of mortality.

Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

COSMOS: the dialysis scenario of CKD-MBD in Europe.

BACKGROUND: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. METHODS: COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. RESULTS: The haemodialysis population in Europe is an aged population (mean age 64.8±14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3±14.3 versus 66.0±13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. CONCLUSIONS: The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

Do ketoanalogues still have a role in delaying dialysis initiation in CKD predialysis patients?

Early versus later start of dialysis is still a matter of debate. Low-protein diets have been used for many decades to delay dialysis initiation. Protein-restricted diets (0.3-0.6 g protein/kg/day) supplemented with essential amino acids and ketoanalogues (sVLPD) can be offered, in association with pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD) patients not having severe comorbid conditions; they probably represent 30-40% of the concerned population. A satisfactory adherence to such dietary prescription is observed in approximately 50% of the patients. While the results of the studies on the effects of this diet on the rate of progression of renal failure remain inconclusive, they are highly significant when initiation of dialysis is the primary outcome. The correction of uremic symptoms allows for initiation of dialysis treatment at a level of residual renal function lower than that usually recommended. Most of the CKD-associated complications of cardiovascular and metabolic origin, which hamper both lifespan and quality of life, are positively influenced by the diet. Lastly, with regular monitoring jointly assumed by physicians and dietitians, nutritional status is well preserved as confirmed by a very low mortality rate and by the absence of detrimental effect on the long-term outcome of patients once renal replacement therapy is initiated. On account of its feasibility, efficacy and safety, sVLPD deserves a place in the management of selected patients to safely delay the time needed for dialysis.

[Dynamics of serum visfatin level after abdominal surgery: a new proinflammatory marker in the early diagnosis?]. / Dynamika zmen sérového visfatinu po abdominálním chirurgickém výkonu: nový proinflamacní marker v casné diagnostice?

BACKGROUND: Visfatin is a newly recognized adipocytokine produced mainly in visceral fat tissue. Beside its effect on insulin receptor, it serves as proinflammatory cytokine and its level can be changed during inflammatory processes. The aim of the study was to analyze dynamics of serum visfatine level in early period after abdominal surgery and compare it with other proinflammatory markers. METHODS AND RESULTS: In prospective cross-sectional study 20 patients after elective laparotomic abdominal surgery (partial colectomy) were enrolled and dynamics of visfatin, leptin, resistin, adiponectin, TNF-α , IL-6 and CRP in period +12, +24, +48 and + 72 hours was monitored. Serum visfatin was elevated already in +24 hrs period after surgery comparing the culmination of serum level of TNF-α and IL-6 12-24 hrs later and CRP even 48-72 hrs later. CONCLUSIONS: Serum visfatin was elevated very early after abdominal surgery and thus its dynamic may be an early predictor of inflammatory processes namely in patients with visceral obesity.

Muscle and fat metabolism in obesity after kidney transplantation: no effect of peritoneal dialysis or hemodialysis.

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 µg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 µmol/L; P < .01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.

Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for chronic kidney disease patients.

Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction.

Anti-SARS-CoV-2 Vaccination and Antibody Response in Patients With Inflammatory Bowel Disease on Immune-modifying Therapy: Prospective Single-Tertiary Study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion. CONCLUSIONS: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.

Cellular and Humoral Immune Responses to SARS-CoV-2 Vaccination in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Knowledge on the immunogenicity of anti-SARS-CoV-2 vaccines in inflammatory bowel disease [IBD] patients is limited. Therefore, SARS-CoV-2-specific T-cell responses and antibodies were analysed in 60 IBD vaccine recipients and 30 controls. METHODS: SARS-CoV-2 IgG antibodies against the viral spike protein were measured at baseline and at 8 and 26 weeks after the second vaccine dose. SARS-CoV-2 IgG antibodies against the nucleocapsid antigens were measured at week 26. A SARS-CoV-2 interferon-gamma released assay [IGRA] was performed in all vaccinees at week 26. RESULTS: At weeks 0 and 8, no differences were found in anti-spike antibodies between cohorts. At week 26, the decrease in antibody levels was more significant in the IBD cohort compared to the healthy cohort, and anti-nucleocapsid antibodies were not detected in either group. At week 26, 16 of 90 [18%] vaccinated individuals had a negative IGRA test result, seven of 90 [8%] were borderline and 67 [74%] had a positive IGRA result; 22 of the 23 individuals with negative or borderline IGRA results belonged to the IBD cohort. However, the overall functional ability of T-lymphocytes to produce interferon-gamma after the unspecific mitogen stimulation was lower in IBD patients. In vaccinated individuals with low or borderline IGRA, treatment with tumour necrosis factor-alpha inhibitors was the most frequent. In individuals with a significant drop in anti-spike antibody levels, plasmatic interferon-gamma concentrations after the specific SARS-CoV-2 stimulation were also insufficient. CONCLUSIONS: Simple humoral and cellular post-vaccination monitoring is advisable in IBD patients so that repeated vaccine doses may be scheduled.

[Kidney transplantation at the Institute for Clinical and Experimental Medicine]. / Transplantace ledviny v IKEM.

BACKGROUND: Kidney transplantation represents the method of choice of end stage renal disease. METHODS AND RESULTS: The program of kidney transplantation was established in 1966 in our centre. In recent years, roughly 200 patients have undergone kidney transplantation annually, and 20-30 of them have received a graft from the living donor. Triple immunosuppressive regimen based on tacrolimus, MMF and steroids is given to majority of patients, in a case of high rejection risk; patients have received the induction protocols with polyclonal or monoclonal antilymphocyte globulins. Acute rejection is not a frequent finding in recent years and has occurred in 15% of cases in the first 3 months, the use of induction immunosuppression has decreased the rejection risk. Valgancyclovir has been used as prophylactic agent to prevent and treat cytomegalovirus infection. The usage of this strategy reduced the incidence of CMV infection below 10%. Kidney transplant recipients suffer from similar comorbidities as other renal patients in the long term, as cardiovascular complications, infections and malignancies. Anemia is a frequent complication in patients with graft dysfunction and erythropoesis stimulating agents have been used in its therapy. The median kidney graft survival is 8 years. CONCLUSIONS: Kidney transplantation is associated with better long-term results when compared with dialysis therapy and thus this method should be offered to all of suitable end stage renal disease patients.

Gender-related determinants of advanced subclinical atherosclerosis in patients undergoing kidney transplantation.

BACKGROUND: Cardiovascular disease caused by atherosclerosis remains a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). We evaluated the potential association of cardiovascular risk factors including asymmetric dimethyl L-arginine (ADMA) and the soluble receptor for advanced glycation end products (sRAGE) with preclinical atherosclerosis in patients undergoing kidney transplantation. PATIENTS AND METHODS: In 92 males and 47 females undergoing the first cadaveric renal transplantation, ADMA, sRAGE and common risk factors including lipid parameters were evaluated as potential predictors of preclinical atherosclerosis defined as the Belcaro score (focused on advanced atherosclerotic changes) measured by ultrasound. RESULTS: The prevalence of atherosclerotic changes was approximately 70% in men and women. In logistic regression, age, history of smoking, presence of diabetes mellitus, and plasma triglycerides were the strongest independent predictors for advanced atherosclerosis in the whole group. In unadjusted analyses advanced atherosclerosis was also associated with sRAGE in men and with the atherogenic index of plasma in women. CONCLUSION: Apart from traditional cardiovascular risk factors, plasma triglycerides were found to be strong and independent predictors of advanced atherosclerosis in patients with ESRD. In addition, sRAGE was associated with atherosclerosis in men and the atherogenic index of plasma in women.