[Efficacy of rituximab in minimal change disease, an atypical renal manifestation of antiphospholipid syndrome]. / Skutecznosc rytuksymabu w leczeniu choroby zmian minimalnych stanowiacej nietypowa nerkowa manifestacje zespolu antyfosfolipidowego.

Antiphospholipid syndrome (APS) is defined as presence of antiphospholipid antibodies along with hypercoagulable events. Renal involvement in APS usually manifests as thromboembolic complications observed in large blood vessels or small intrarenal vessels (APS nephropathy). We report a rare case of glomerulitis associated with APS and being characterised by features different from typical APS nephropathy. A CASE REPORT: A 23-years-old patient was admitted to the nephrology department with steroid-sensitive, steroid-dependent nephrotic syndrome secondary to minimal change disease, first diagnosed at the age of 18 months. Subsequent thromboembolic events, such as deep vein thrombosis, unilateral thrombosis of the popliteal artery, and pulmonary embolism, led to the diagnosis of antiphospholipid syndrome. The patient also had a history of acute kidney injury. On the day of admission, the patient had normal renal function and was taking an increased dose of prednisone owing to nephrotic syndrome relapse. In the past, attempts to reduce the dosage of glucocorticoids were made using cyclophosphamide, cyclosporin A, mofetil mycophenolate, and their combinations. It rendered ineffective as nephrotic syndrome relapses occurred. The patient's eligibility for the rituximab treatment was established in a series of diagnostic tests which excluded any contraindications. No adverse effects were observed during or after intravenous infusion of the drug. CONCLUSIONS: The case emphasizes a rare renal clinical manifestation of APS in nephrologist's practice. The combination of anti-CD20 monoclonal antibody and anticoagulants is highly likely to be the optimal solution for this problem.

Novel Complement Factor B Gene Mutation Identified in a Kidney Transplant Recipient with a Shiga Toxin-Triggered Episode of Thrombotic Microangiopathy.

BACKGROUND Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disorder characterized by over-activation and dysregulation of the alternative complement pathway. The clinical presentation of the disease comprises thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. In most cases, aHUS is caused by genetic mutations in components of the alternative complement pathway. The risk of graft loss in patients after kidney transplantation with aHUS is dependent on the type of genetic mutation. CASE REPORT We present a case of a 32-year-old patient after a second kidney transplantation with atypical hemolytic uremic syndrome, whose clinical manifestation was triggered by the Shiga toxin-producing E. coli infection. Genetic testing revealed a new mutation (p.I342T) in the gene encoding complement factor B (CFB). Since 2 causative variants for aHUS have been described in the same exon of CFB gene, it might be supposed that the p.I342T variant has similar deleterious effects on CFB function. Despite the implemented treatment, graft function deteriorated and the patient had to return to a hemodialysis program and is currently on a waiting list for a third kidney transplant. The presence of the gene variant with increased susceptibility for aHUS and its recurrence after kidney transplantation makes the patient a good candidate for therapy with complement factor C5 inhibitors during and after the planned kidney transplantation. CONCLUSIONS Our case confirms the importance of genetic testing in patients with any sign of thrombotic microangiopathy. The finding of Shiga toxin-induced HUS with typical clinical course should not limit our vigilance of complement-mediated HUS with high risk of renal failure.

Different Effects of Empagliflozin on Markers of Mineral-Bone Metabolism in Diabetic and Non-Diabetic Patients with Stage 3 Chronic Kidney Disease.

Background and objectives: Treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors decrease tubular reabsorption of phosphate, which may explain the reduction of bone mineral density and an excess of bone fractures observed in some studies with this class of drugs. Since an increased risk of bone fractures may also be a result of diabetes itself, our study aimed to compare the effect of empagliflozin on the markers of mineral-bone metabolism between diabetic (DKD) and non-diabetic (ND-CKD) patients with stage 3 chronic kidney disease (CKD). Materials and Methods: Forty-two patients with stage 3 CKD and A2 albuminuria, including 18 with DKD and 24 ND-CKD, were investigated. All subjects received 10 mg empagliflozin for 7 days. Serum calcium, phosphate, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF-23 and urine calcium, phosphate, albumin and the renal tubular maximum reabsorption rate of phosphate to the glomerular filtration rate (TmP-GFR) were measured before and after empagliflozin administration. Differences in biomarkers response to empagliflozin between DKD and ND-CKD were the main measures of outcome. Results: There was a significant increase of PTH, FGF-23 and phosphate in DKD but not in ND-CKD whereas BAP and TmP/GFR did not change in either group. The reduction of albuminuria was only significant in ND-CKD. Conclusions: The effect of SGLT2 inhibitor on serum mineral and bone markers and on albuminuria in patients with CKD may be differently modified by the presence of diabetes mellitus.

Losartan and Eprosartan Induce a Similar Effect on the Acute Rise in Serum Uric Acid Concentration after an Oral Fructose Load in Patients with Metabolic Syndrome.

INTRODUCTION: Excessive intake of fructose increases serum uric acid concentration. Hyperuricemia induces a negative effect on atherosclerosis and inflammation. Hyperuricemia is common in patients with arterial hypertension. Several antihypertensive drugs including diuretics increase serum uric acid concentration. In contrast, the angiotensin II receptor antagonist (ARB) losartan was found to lower serum uric acid though it may increase renal excretion while other ARBs showed mostly a neutral effect. In this study, effects of two AT1 receptor antagonists losartan and eprosartan on serum uric acid changes induced by oral fructose load were directly compared. METHODS: The randomized, crossover, head-to-head comparative study comprised 16 ambulatory patients (mean age 64.5 ± 9.8 years). The patients fulfilled AHA/NHLBI 2005 criteria of metabolic syndrome. A daily single morning dose of each study drug (50 mg of losartan or 600 mg of eprosartan) was given during two 3-month periods in a random order separated by 2-week washout time. The oral fructose tolerance test (OFTT) was performed at baseline and after each two 3-onth treatment periods. Before and during OFTT, urine excretion of uric acid and creatinine was assessed in the first morning portion of urine. Blood samples for the measurement of serum uric acid and lipids were taken at baseline and 30, 60, and 120 minutes after oral intake of 75 g of fructose. RESULTS: After 3-month treatment with eprosartan and losartan, both systolic and diastolic blood pressure decreased significantly and to a similar extent. After the treatment, serum uric acid and its baseline and postfructose urine excretion were unchanged. No significant changes of plasma lipids before and after OFTT were observed throughout the study. CONCLUSIONS: The study showed that in patients with hypertension and metabolic syndrome, both losartan and eprosartan have a neutral effect on fasting and postfructose load serum uric acid concentration and its urinary excretion. This trial is registered with NCT04954560.

Secondary Hemophagocytic Lymphohistiocytosis Complicated by a Cavitary Lung Lesion in a Kidney Transplant Recipient.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon life-threatening condition caused by an uncontrolled immunological response. It can develop secondary to malignancies, infections, systemic diseases, and immunosuppression. Multiple risk factors may present in kidney transplant recipients; however, the cases of HLH in this population have been described sparsely. We report a case of a 39-year-old female kidney transplant recipient who presented to the hospital nearly 3.5 years after the transplantation with general malaise, recent history of weight loss, fevers, and persistent anemia. Laboratory tests showed pancytopenia, hyperferritinemia, hypertriglyceridemia, and increased activity of lactate dehydrogenase. A bone marrow aspiration revealed hemophagocytosis, which led to the diagnosis of HLH. Therapy consisting of high-dose steroids and plasma exchanges was administered, resulting in a significant improvement of blood count parameters and the patient's general condition. While searching for the triggering disease, a single cavitary lesion in the right lung was revealed in a chest radiograph. Computed tomography scan, bronchoscopy, and additional laboratory testing did not reveal a definitive cause of the lesion. We suspect that the lesion may be a consequence of HLH. The patient was disqualified from thoracic surgery due to multiple comorbidities. Even though HLH is a rare condition, it should be taken into consideration in a kidney transplant patient presenting with unspecific symptoms accompanied by a bicytopenia. It has an unpredictable course that often results in serious complications. Thus close follow-up of the patient and a wide array of imaging and laboratory tests remain crucial.

Effect of Short-Term Cold Exposure on Central Aortic Blood Pressure in Patients with CKD.

OBJECTIVES: Study determined effects of arterial hypertension and impaired kidney function on acute cold exposure induced changes in peripheral and central aortic blood pressure (BP). METHODS: Five-six subjects were divided into 3 groups including 20 hypertensive patients with normal kidney function (AH-non-CKD), 20 patients with hypertension and CKD (AH-CKD) stage 3b-4 and 16 healthy normotensive subjects (C). Baseline BP, central BP, and central pulse pressure, unadjusted augmentation index (AI) and central augmented pressure were assessed by applanation tonometry (SphygmoCor) before entering the room with constant temperature -10°C (°C), after 10 min in the cold room and in same conditions in room temperature. RESULTS: Cold exposure led to significant increase of central aortic, systolic, and diastolic BP in both AH-non-CKD (p < 0.01) and AH-CKD (p < 0.001). The central aortic BP did not change in healthy subjects. The increase of central aortic systolic blood pressure was significantly larger in AH-CKD compared to AH-non-CKD group (p = 0.0002). Increase of aortic central and brachial systolic and diastolic BP was significantly larger in AH-CKD and AH-non-CKD patients than in controls. AI increased and subendocardial viability ratio and heart rate decreased after cold exposure in all groups. Central aortic and brachial rate pressure product increased by approximately 2,300 bpm × mm Hg (p < 0.001) and 1,600 bpm × mm Hg (p < 0.001), respectively, in the AH-CKD group and by 1,000 bpm × mm Hg (p = 0.007) and 500 bpm × mm Hg (p = 0.19) in AH-non-CKD group after cold exposure. CONCLUSION: Short-term cold exposure induces larger increase of brachial and central aortic BP in patients with arterial hypertension than in healthy subjects. The changes in central aortic pressure are augmented in hypertensive patients with impaired kidney function.

'I hear and I forget. I see and I remember. I do and I understand.'- incorporating high-fidelity medical simulation into the undergraduate nephrology course.

BACKGROUND: Medical simulation is a teaching method, which enables the development of clinical skills by implementing a simulation scenario in a true-to-life environment, but without exposing patients to any risk. So far, there has been no information on the use of high-fidelity simulation in undergraduate clinical nephrology teaching. Aim of this study was to analyze students' opinions and reactions to the simulation module in nephrology. METHODS: The survey consisting of the Satisfaction with Simulation Experience Scale (SSES) and open-ended question concerning the overall impression of classes was conducted among 103 5th year medical students, who took part in the simulation training in nephrology. SSES consisted of three parts (debriefing, reasoning, education). Statements from the open-ended question were interpreted by means of the Atlas.ti software for qualitative data analysis. RESULTS: The overall score for simulation classes was 4.39 ± 0.69 points. Students rated debriefing, reasoning and education at 4.43 ± 0.78, 4.32 ± 0.7 and 4.39 ± 0.73 points, respectively. 87.4% and 84.5% of participants agreed that simulation developed their 'clinical reasoning' and 'decision-making' skills in nephrology, respectively. Thematic analysis revealed that students evaluated the module as 'interesting', 'useful' and 'informative', but they found number of classes significantly insufficient. Students pointed out that due to the small emphasis placed on practical aspects in the existing curriculum e.g. routes of drug administration and conversion of doses, they could not fully benefit from simulation. CONCLUSION: Medical simulation is a valuable constituent of the nephrology course. Putting greater emphasis on practical aspects from the beginning of training may enable students to benefit more from simulation modules.

Diagnosis and treatment of type 2 diabetes mellitus in patients with chronic kidney disease and eGFR < 60 mL/min - a position statement of the Polish Society of Nephrology Working Group on Metabolic and Endocrine Disorders in Kidney Diseases.

Diabetes mellitus is one the most frequent co-morbid conditions in patients with chronic kidney disease (CKD), frequently leading to chronic kidney failure. Progression of CKD accelerates several metabolic disorders, predominantly those related to abnormalities of carbohydrate metabolism. Patients with CKD are usually characterised by an insulin resistance additionally aggravated by several co-morbid conditions (for example chronic low-grade inflammation). Treatment with anti-diabetic medications in patients with CKD remains a challenge because, along with the disease progression, the dosing of several drugs needs to be adjusted to the reduced kidney function (especially those that are excreted intact with urine or as active metabolites). Progression of CKD also increases the risk of hypoglycaemia in patients treated with anti-diabetic drugs, and other adverse drug reactions may occur more frequently. Usefulness of the new generation drugs has not yet been verified in patients with advanced kidney disease (although some of them act through kidney-related mechanisms). The current position statement of the Polish Society of Nephrology Working Group provides practical recommendations for the diagnosis and treatment of type 2 diabetes mellitus in patients with CKD and reduced kidney function.

Effects of a Structured Physical Activity Program on Serum Adipokines and Markers of Inflammation and Volume Overload in Kidney Transplant Recipients.

BACKGROUND Kidney transplantation (KTx) reverses most abnormalities related to chronic kidney disease (CKD), but sedentary lifestyle persists in most kidney graft recipients. Physical inactivity has been associated with altered adipokine profile and inflammation in CKD. We postulated that increased physical activity achieved through an individually-tailored program can reverse these changes. MATERIAL AND METHODS We included 25 clinically stable KTx recipients at least 12 months after transplantation and with eGFR >30 mL/min and 15 age-matched non-dialysis patients with CKD stage 3. Body composition, pattern of daily physical activity, and serum concentrations of leptin, adiponectin, NT-proBNP, and hsCRP were assessed at baseline. All patients in both groups participated in a 12-week supervised exercise program with short cell phone text reminders. All measurements were repeated after 3 months. RESULTS Active energy expenditure increased significantly during the 3 months in both the KTx and CKD patients, compared with baseline by 47% (p<0.001) and 20% (p=0.01), respectively. Time spent daily on physical activity was also increased (129±83 vs. 194±142 and 81±56 vs. 124±57 min, respectively, p<0.001). Adipose tissue mass decreased significantly in the KTx group (from 40.8±11 to 38.5±10.3 kg, p=0.01). Serum leptin decreased significantly in both KTx and CKD patients (from 11.5±7.0 to 10.0±5.6, p=0.03 and from 14.1±8.3 to 12.2±6.1 ng/mL, p=0.01, respectively). Serum adiponectin increased only in the KTx group (from 1900±953 to 2015±1133 ng/L, p=0.004). Serum CRP decreased in both groups (from 15.1±5.2 to 14.0±5.6 mg/L, p=0.01 in the KTx group and from 16.5±3.9 to 15.4±4.3 mg/L in the CKD group p=0.05). NTpro-BNP was unchanged during the study. CONCLUSIONS Increased physical activity induces beneficial effects on adipokine profile and inflammation but does not seem to affect volume overload in kidney transplant recipients and CKD patients.

Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study.

BACKGROUND: The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy. METHOD: The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile. RESULTS: Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients (P=0.02). After statin therapy, low-density lipoprotein cholesterol (P<0.0001), C-reactive protein (P=0.03), von Willebrand factor (P=0.03) and vascular endothelial growth factor (P<0.01) decreased and flow-mediated vasodilation improved (P<0.001). Statins had no significant effect on blood pressure. CONCLUSIONS: Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.

Simultaneous Improvement of Habitual Physical Activity and Life Quality in Kidney Transplant Recipients Involved in Structured Physical Activity Program.

OBJECTIVES: The aim of the study was to compare the effects of a physical activity program on daily physical activity and quality of life in kidney transplant (KTx) recipients and in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: The study group consisted of 24 KTx recipients and 15 patients with stage 3 to 4 CKD. Habitual physical activity was monitored for 72 hours. Individualized structured programs of increased physical activity were prepared based on baseline physical performance. The measurements were repeated after 1 and 3 months. Participants completed the 36-item Short Form Health Survey questionnaire and an International Physical Activity Questionnaire at baseline and after 1, 2, and 3 months. RESULTS: Physical activity duration and total energy expenditure significantly increased after 3 months in both KTx recipients (from 126 ± 87 to 200 ± 132 min/d, P = .001, and from 1.73 ± 0.37 to 2.24 ± 0.59 cal/min, P < .001, respectively) and CKD patients (from 79 ± 78 to 129 ± 114 min/d, P < .001, and from 1.5 ± 0.5 to 1.92 ± 0.47 cal/min, P < .001, respectively). Short Form Health Survey total score and physical component scale score improved significantly in both groups. Mental component scale score increased significantly only in KTx patients. CONCLUSION: Increased physical activity induces similar beneficial effects on total and physical activity component of quality of life and habitual daily activity in CKD and KTx patients.

Effects of a Structured Physical Activity Program on Habitual Physical Activity and Body Composition in Patients With Chronic Kidney Disease and in Kidney Transplant Recipients.

OBJECTIVES: In this study, we compared the effects of an individualized physical activity program on lifestyle, metabolic profile, body composition, and quality of life in kidney transplant recipients and patients with chronic kidney disease. MATERIALS AND METHODS: Our study included 24 kidney transplant recipients and 15 patients with chronic kidney disease at stage 3/4. Body composition (impedance spectroscopy) and habitual physical activity (accelerometry) assessed at baseline were used to prepare the individualized physical activity program. Participants received repeated training, which was supervised during the first 2 weeks, followed by short message service reminders. Measurements were repeated after 1 and 3 months. RESULTS: Time spent daily on physical activity and total energy expenditure increased in kidney transplant recipients (from 126 ± 87 to 200 ± 132 min/day [P = .001] and from 1.73 ± 0.37 to 2.24 ± 0.59 cal/min [P < .001]) and in patients with chronic kidney disease (from 79 ± 78 to 109 ± 114 min/day [P < .001] and from 1.5 ± 0.5 to 1.92 ± 0.47 cal/min [P < .001]). Adipose mass (40.8 ± 11.5 vs 38.5 ± 10.3 kg; P = .01), total body water (38.1 ± 9.1 vs 37.3 ± 9.7 L; P = .01), and fat tissue index (14.3 ± 3.7 vs 13.5 ± 3.1 kg/m2; P = .009) decreased significantly only in kidney transplant recipients. Body cell mass decreased in patients with chronic kidney disease. Significant changes of estimated glomerular filtration rates were observed in kidney transplant recipients. CONCLUSIONS: Increased physical activity achieved through structured exercise programs induced beneficial effects on metabolic profile and body composition in patients with chronic kidney disease, with even greater benefits in kidney transplant recipients.

Diagnosis and Treatment of Metabolic Acidosis in Patients with Chronic Kidney Disease - Position Statement of the Working Group of the Polish Society of Nephrology.

Metabolic acidosis is commonly found in patients with chronic kidney disease (CKD), and its causes are: impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food. As the consequence, numerous metabolic abnormalities develop, which may lead to dysfunction of several organs. In observational studies, it has been found that CKD patients with metabolic acidosis are characterised by faster progression of kidney disease towards end stage kidney failure, and by increased mortality. Results of interventional studies suggest that alkali therapy in CKD patients slows progression of kidney disease. In view of these facts, the members of "The Working Group of the Polish Society of Nephrology on Metabolic and Endocrine Abnormalities in Kidney Diseases" have prepared the following statement and guidelines for the diagnosis and treatment of metabolic acidosis in CKD patients. Measurement of bicarbonate concentration in venous plasma or venous blood to check for metabolic acidosis should be performed in all CKD patients and metabolic acidosis in these patients should be diagnosed when the venous plasma or venous blood bicarbonate concentration is lower than 22 mmol/l. In patients with metabolic acidosis and CKD, oral sodium bicarbonate administration is recommended. The goal of such a treatment is to achieve a plasma or blood bicarbonate concentration equal to or greater than 22 mmol/l.

Effect of atorvastatin on iron metabolism regulation in patients with chronic kidney disease - a randomized double blind crossover study.

INTRODUCTION: To determine the effect of 6-month administration of atorvastatin on hepcidin and hemojuvelin levels, inflammatory parameters and iron metabolism in patients with chronic kidney disease (CKD) stages 3 and 4. METHODS: Thirty six statin- and erythropoiesis-stimulating agent-naive patients with CKD stages 3 and 4 and LDL cholesterol ≥100 mg/dl received atorvastatin or placebo for two 6-month periods in a double blind, randomized crossover study. Hepcidin, hemojuvelin, hsCRP, IL-6, hemoglobin, red blood cell distribution width, iron, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) were measured before and after each treatment period. RESULTS: Hepcidin decreased (from 102 [307] to 63 [170] pg/ml (p > .001)) in the course of statin therapy but remained unchanged after placebo administration (173 [256] to 153 [204] pg/ml, respectively). Hemojuvelin did not change after either part of the study. Both IL-6 and hsCRP decreased following statin therapy (from 8.7 [12.0] to 8.1 [13.9] pg/ml; p = .04 and from 4.7 [4.0] to 4.0 [3.6] mg/l; p = .4, respectively), but did not change after placebo administration. Blood hemoglobin increased slightly but significantly after 6-month statin therapy (from 11.6 ± 1.6 to 11.9 ± 1.5 g/dl, p = .002), and was unchanged after placebo treatment. TIBC and UIBC increased significantly after 6-month statin therapy, and serum iron also tended to increase. The change of eGFR during the study did not differ between the two treatment periods. CONCLUSIONS: Statin may have a small but potentially beneficial effect on serum hepcidin, which may lead to improvement of anemia control in CKD patients.

New markers of urinary tract infection.

Urinary tract infection (UTI) is the most common bacterial infection independent of age. It is also one of the most common causes of hospitalizations for infections among elderly people and the most common indication for antibiotic prescriptions in primary care. Both diagnostics and management of lower and upper urinary tract infections provide challenges in clinical practice due to their high prevalence and recurrence, and worldwide increase of antibiotic resistance. The clinical symptoms of UTI are often uncharacteristic or asymptomatic. The accurate diagnosis and early treatment are crucial due to risk of septicaemia and long-term consequences. Currently the diagnosis of urinary tract infection is based on the presence of clinical symptoms in combination with the results of nitrite strip test indicating the presence of bacteria in urine and semi-quantitative measurement of white blood cells count in urine. Although urine culture is the gold standard in UTI diagnostics it is both time-consuming and costly. Searching for novel biomarkers of UTI has attracted much attention in recent years. The article reviews several promising serum and urine biomarkers of UTI such as leukocyte esterase, C-reactive protein, procalcitonin, interleukins, elastase alpha (1)-proteinase inhibitor, lactofferin, secretory immunoglobulin A, heparin-binding protein, xanthine oxidase, myeloperoxidase, soluble triggering receptor expressed on myeloid cells-1, α-1 microglobulin (α1Mg) and tetrazolium nitroblue test (TNB).

Plasma Desphospho-Uncarboxylated Matrix Gla Protein as a Marker of Kidney Damage and Cardiovascular Risk in Advanced Stage of Chronic Kidney Disease.

BACKGROUND/AIMS: Desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) is formed as a result of vitamin K insufficiency. The aim of this study was to investigate the association between plasma dp-ucMGP, kidney function and cardiovascular risk factors before and after 9-months substitution of vitamin K2 in non-dialysis patients with chronic kidney disease (CKD) stage 4 and 5. METHODS: 38 CKD patients were supplemented for 270±12 days with 90 µg vitamin K2 and 10 µg cholecalciferol or 10 µg cholecalciferol alone. At baseline and at follow-up circulating calcium, phosphate, lipids, hemoglobin, albumin and total protein, dp-ucMGP, osteoprotegerin, fetuin A, osteocalcin and fibroblast grown factor 23 (FGF-23) were assessed. Proteinuria was assessed in the first morning void. RESULTS: Baseline plasma dp-ucMGP was 1018.6±498.3 pmol/l and was significantly higher in patients at stage 5 CKD (1388.3 ±505.4 pmol/l) than at stage 4 (885.1±419.7 pmol/l), p=0.04. Vitamin K2 supplementation resulted in a decrease of dp-ucMGP level by 10.7%. Plasma dp-ucMGP was positively associated with proteinuria, serum creatinine, PTH and FGF-23; and inversely associated with glomerular filtration rate, serum hemoglobin and albumin. CONCLUSIONS: High dp-ucMGP level, reflecting a poor vitamin K status seems to be associated with kidney damage and may be also a marker of cardiovascular risk in CKD patients. Supplementation with vitamin K2 may improve the carboxylation status of MGP.

Utility of copeptin and standard inflammatory markers in the diagnostics of upper and lower urinary tract infections.

BACKGROUND: A new serum marker of inflammation copeptin (CPP) a stable C-terminal pro-vasopressin was assessed along with conventional markers such as C-reactive protein (CRP), procalcitonin (PCT) and IL-6 to discriminate between lower and upper bacterial urinary tract infections (UTI). METHODS: Study population comprised 45 patients including 13 with lower UTI (L-UTI) and 32 with upper UTI (U-UTI) and 24 healthy controls. Serum markers, blood cultures and urine cultures were assessed before commencing antibiotic treatment and repeated 24, 48 h and 7 days thereafter. Receiver operating curves (ROC) were plotted to assess a diagnostic utility of different inflammatory markers. RESULTS: Before antibiotic therapy all inflammatory markers including serum CPP (2821.1 ± 1072.4 pg/ml vs. 223.8 ± 109.3 pg/ml; p < 0.05) were higher in UTI than in controls. CPP was not different between L- and U-UTI (2253 ± 1323 pg/ml vs 3051 ± 1178 pg/ml; p = 0.70) despite significant differences in hsCRP (2.09 ± 1.7 mg/dl vs 127.3 ± 62.4 mg/dl; p < 0.001), PCT (0.05 ± 0 vs 5.02 ± 0.03 ng/ml p < 0.001) and IL-6 (22.5 ± 1.6 vs 84.8 ± 67 pg/ml p < 0.001). For U-UTI the areas under the ROC curves were 1.0 for both hsCRP and CPP, 0.94 for PCT and 0.7 for IL-6 and for L-UTI 0.571, 1, 0.505 and 0.73, respectively. After 7 days of treatment all markers decreased in parallel to clinical response. CONCLUSION: Although elevated serum copeptin may become a marker of UTI it seems to be inferior compared to traditional serum inflammation markers for differentiation of bacterial infections involving upper and lower urinary tract.

Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5.

INTRODUCTION: Observational studies have shown that high dietary intake of vitamin K2 is associated with reduced risk of coronary vascular disease and vascular calcification. OBJECTIVES: We assessed the effect of vitamin K2 substitution on the progression of atherosclerosis and calcification in nondialyzed patients with CKD stages 3-5. PATIENTS AND METHODS: The study included 42 nondialyzed patients with CKD. The following measurements were taken at baseline and after 270 ±12 days of supplementation with vitamin K2 at a dose of 90 µg (menaquinone, MK-7) together with 10 µg of cholecalciferol (K+D group) or 10 µg of cholecalciferol (group D): common carotid intima-media thickness (CCA-IMT), coronary artery calcification score (CACS), basic biochemical parameters, lipids, and calcification modulators: matrix Gla protein (MGP), desphosphorylated-uncarboxylated MGP (dp-ucMGP), osteoprotegerin (OPG), fetuin A, osteocalcin (OC), and fibroblast growth factor 23. RESULTS: The increase of CCA-IMT was significantly lower in the K+D group compared with the D group: from 0.95 ±0.2 mm to 1.01 ±0.3, P = 0.003 vs from 1.02 ±0.2 mm to 1.16 ±0.3, P = 0.003 (ΔCCA-IMT, 0.06 ±0.08 vs 0.136 ±0.05 mm, P = 0.005, respectively). The increase in CACS was slightly lower in the K+D group than in the D group (ΔCACS, 58.1 ±106.5 AU vs 74.4 ±127.1 AU, P = 0.7). In the K+D group, a significant decrease in the level of dp-ucMGP and total OC was observed. CONCLUSIONS: A 270-day course of vitamin K2 administration in patients with CKD stages 3-5 may reduce the progression of atherosclerosis, but does not significantly affect the progression of calcification. Vitamin K2 significantly changes the levels of calcification promoters and inhibitors: dp-ucMGP, OC, and OPG.

Diabetes modifies effect of high-phosphate diet on fibroblast growth factor-23 in chronic kidney disease.

CONTEXT: The pathophysiology of calcium-phosphate disturbances in diabetic (DM) kidney disease differs from that in non-DM chronic kidney disease (CKD). OBJECTIVE: We compared the effect of a 6-day high-phosphate diet on serum fibroblast growth factor-23 (FGF-23) and other parameters of calcium-phosphate metabolism in DM and non-DM CKD patients. DESIGN AND SETTING: This was a prospective interventional study in a research center setting. PARTICIPANTS, INTERVENTION, AND MEASURES: Twenty-six nondialysis patients with stages 3-5 CKD and albuminuria less than 300 mg/g creatinine were recruited from February 2011 to November 2012 (15 DM, 11 non-DM). All patients received a high-phosphate diet (1800 mg/d) for 6 days. At baseline, day 3, and day 7 serum FGF-23, PTH, Ca, P, 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, monocyte chemoattractant protein-1, and calcium and phosphate urine excretion were measured. RESULTS: In DM CKD patients, serum calcium was lower on days 3 and 7 vs baseline (P < .01, respectively), and in non-DM patients, it was unchanged. Serum phosphorus increased significantly only in non-DM patients on days 3 and 7 vs baseline (P < 0.01, respectively). Serum PTH was higher in the DM group on day 7 vs baseline (P = .04). Plasma 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, and serum monocyte chemoattractant protein-1 were unchanged in both groups. Serum FGF-23 increased in DM patients, from baseline to day 3 (58.1 ± 52.7 and 91.6 ± 71.1 pg/mL, P = .001) but later tended to decrease. In non-DM patients, there was a steady increase of FGF-23 between baseline and day 7 (75 ± 84.3 to 176 ± 197 pg/mL, P = .04). Urine phosphate excretion was significantly higher on day 7 in DM patients only (P < .05). CONCLUSIONS: PTH seems to play the major role in the regulation of phosphate excretion in DM CKD. The role of FGF-23 in phosphate disposal in DM CKD remains debatable.