Haematological disorders following kidney transplantation.

Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management.

How to assess kidney function in oncology patients.

Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.

[Circulating bone turnover markers and their relationships in hemodialysis patients with vitamin D deficiency].

OBJECTIVE: Introduction: Mineral homeostasis is achieved through a complex interplay of several feedback processes involving primarily the bone, intestine and kidney, regulated by different proteins acting on endocrine, paracrine or autocrine levels. The dysregulation of these processes in chronic renal failure, called kidney disease (CKD) - mineral and bone disorder (CKD-MBD), although apparent, is still poorly understood. The aim: The aim of the study was an analysis of potential relationships between selected biomarkers of CKD-MBD in maintenance hemodialysis (HD) patients. PATIENTS AND METHODS: Material and Methods: In the first part of this cross-sectional study, the 25(OH)D serum concentrations were measured in 115 HD vitamin D naïve patients from 5 dialysis units located in central Poland. Thereafter in 81 patients (49 men, 32 women, aged 67 ± 13 years) with vitamin deficiency (25(OH)D <20 ng/ml) serum concentrations of 25(OH)D, 1,25(OH)2D, intact parathyroid hormone (iPTH), intact FGF23, sclerostin (SCL), osteocalcin (OC), and C-terminal telopeptide of type I collagen (CTX1) were determined. RESULTS: Results: Serum levels of both 25(OH)D and 1,25(OH)2D were low (mean values 13.4±6.72 ng/ml and 12.9 ± 9.08 pmol/l, respectively). While serum 25(OH)D correlated only with a declared time spent outside (r= 0.411; p=0.000139), serum 1,25(OH)2D was related to diuresis (r= 0.289; p=0.009), and negatively to time on dialysis (r= -0.272; p=0.014) , serum phosphate (r= -0.393; p=0.000289), FGF23(r= -0.295; p=0.008), and SCL (r= -0.260; p=0.019). There was a marked dispersion of FGF-23 serum levels across the group (mean 823±5647, median 379 pg/ml) , and - as expected - they correlated highly with phosphate (r= 0.549, p=0.000), calcium (r= 0,328, p=0,003), OC (r=0.479; p=0.000), and negatively with z 1,25(OH)2D (r= -0.295, p=0.008). Mean serum SCL levels (89.2±46.7, median 81.9 pmol/l) were 3x higher than in general population, and correlated highly positively with dialysis vintage (r=0.402; p<0.001), age (r=0.356; p=0.001), as well as negatively with 1,25(OH)2D (r= -0.260; p=0.019) and CTX1 (r= -0.293; p=0.008). CONCLUSION: Conclusions: In our hemodialysis population, in addition to profoundly impaired 1,25(OH)2D synthesis, there is also a widespread prevalence of 25(OH)D deficiency. The patients have also markedly increased serum bone-secreted proteins, FGF23, and SCL, which regulate mineral and bone metabolism and are associated with the systemic side effects of uremia. All these hormones interact one with the other, creating a sophisticated cross-talk between the bone, intestine, and the kidney.

[Toxic alcohol poisonings].

Accidental or intentional poisonings with ethylene glycol or methanol constitute a serious toxicological problem in many countries. Both alcohols are quickly metabolized by alcohol dehydrogenase to toxic metabolites responsible for high anion gap severe metabolic acidosis and profound neurological, cardiopulmonary, renal disturbances and death. In the early period, the competing inhibition the alcohol dehydrogenase with ethanol or fomepizol may successfully prevent the formation of the toxic metabolites. Once severe acidosis develops an emergency hemodialysis is required.

[Age-related kidney problems]. / Problemy nefrologiczne zwiazane z wiekiem.

Kidney diseases, with some exceptions, are diseases of the elderly. During last century mortality due to infections and injuries has gradually decreased and a longer life expectancy increased a rate of chronic diseases. Diabetes, hypertension and atherosclerosis have become most common causes of kidney diseases. A gradual nephrons loss in aging kidneys causes them more susceptible to acute injury as well as fastens the progression of their chronic disease. This leads to the rapid increase in the incidence of kidney diseases with aging. This paper discusses the process of kidney senescence and its influence on the course of kidney disease as well as the differences in the treatment of patients over 65 years.

[Acute kidney injury after hematopoietic cell transplantation]. / Ostre uszkodzenie nerek po przeszczepieniu komórek hematopoetycznych.

Stem cell transplantation is now a routine and successful therapeutic method in many hematopoietic disorders and cancers. Unfortunately, toxicity of the procedure significantly worsens the outcomes, with acute and chronic kidney injury among the others. Etiology of kidney failure is multifactorial with nephrotoxicity of drugs, septic complications, sinusoidal occlusion syndrome, thrombotic microangiopathy and acute/chronic graft-versus-host disease (GvHD). Understanding these syndromes enables early recognition and proper intervention that can reduce incidence and severity of kidney injury and improve outcomes.

[Mineral and bone disorder in chronic kidney disease]. / Zaburzenia mineralno-kostne w przewleklej chorobie nerek.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is characterized by at least one ofthefollowing: 1. biochemical abnormalities in calcium, phosphate, parathormone (PTH) and vitamin D metabolism; 2. renal osteodystrophy; and 3. cardiovascular or other soft tissue calcifications. All these abnormalities are interrelated and significantly contribute to the increased morbidity and mortality in patients with CKD.

[Classification, epidemiology and etiology of chronic kidney disease]. / Klasyfikacja, epidemiologia i przyczyny przewleklej choroby nerek.

Chronic kidney disease (CKD) poses an important health problem. It is a progressive disease with a high risk of cardiovascular complications. In this paper the new classification and diagnostic criteria established in 2012 by Kidney Disease Improving Global Outcomes (KDIGO) are shortly overviewed.

Cholecalciferol vs. Small Doses of Alfacalcidol vs. Placebo in Chronic Kidney Disease Patients on Hemodialysis: A Randomized Parallel Group Study.

BACKGROUND: The ability of extrarenal tissues to convert 25(OH)D (calcidiol) into 1,25(OH)2D (calcitriol) and dependence of the conversion on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both: 25(OH)D and 1,25(OH)2D. The primary aim of the study was to compare effects of small doses of cholecalciferol (12,000 IU/week) with frequently used in Europe, small doses of alfacalcidol (1.5 µg/week) or placebo, given for 12 weeks, on serum 1,25(OH)2D in hemodialysis patients with 25(OH)D deficiency. Secondary outcomes were changes in serum calcium, phosphate, 25(OH)D, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and sclerostin during the treatment. METHODS: This was a prospective, randomized, partly double-blind (cholecalciferol vs. placebo) study. Out of 522 patients dialyzed in 5 centers in the Mazovian Province, 93 gave informed consent and met the inclusion criteria: any vitamin D metabolites and calcimimetics naïve; no history of liver or intestinal disease; serum 25(OH)D <20 ng/ml, iPTH <1,000 ->110 pg/ml, calcium <10.2, and phosphate <6.8 mg/dl. The subjects were stratified by serum iPTH, then randomized into 3 groups according to the treatment. RESULTS: To our knowledge, this is the first study comparing head-to-head these drugs in the hemodialysis population. There were no significant differences between the groups at baseline. 81 patients completed the study. Cholecalciferol normalized serum 25(OH)D, with a mean rise from 12.9 ± 6.7 to 31.3 ± 10.1 ng/ml (p < 0.0001). This was accompanied by a marked increase of 1,25(OH)2D from 13.8 ± 9.3 to 25.1 ± 14.2 pmol/l (p < 0.0001). A rise in serum 1,25(OH)2D was also observed in alfacalcidol treated patients, however much smaller (from 13.5 ± 10.1 to 18.5 ± 11.0 pmol/l; p = 0.02). Neither cholecalciferol nor alfacalcidol treatment resulted in significant changes in serum PTH and the remaining parameters. CONCLUSIONS: In most patients, treatment with cholecalciferol in a 12,000 IU/week dose permits safe correction of 25(OH)D deficiency and is more effective than 1.5 µg/week dose of alfacalcidol in rising serum 1,25(OH)2D. This, together with a lack of influence on circulating iPTH the usefulness of such small alfacalcidol doses in hemodialysis patients is debatable.

Dosing of antibiotics in critically ill patients: are we left to wander in the dark?

Critically ill patients are frequently affected by acute kidney injury accompanied by dysfunction of other systems and organs. Sepsis is common in this population and remains a major cause of multiorgan dysfunction syndrome, indicating a crucial role in efficient antibiotic treatment. However, such treatment is particularly difficult due to altered pharmacokinetic profile in these patients, dynamic changes in their clinical status and, in many cases, need for renal replacement therapy (RRT). Current guidelines concerning the dosing of antibiotics in this patient population are not particularly reliable because they are based on studies involving small and heterogeneous groups of patients, often treated with different RRT modalities. Our paper reviews the basic pharmacokinetic and pharmacodynamic parameters as well as other factors that should be considered while devising a proper therapeutic approach for this patient population.

[The results of treatment patients with hepatorenal syndrome. The analysis of 65 cases]. / Wyniki leczenia zespolu watrobowo-nerkowego. Analiza 65 przypadków.

We analysed medical documentation of 65 patients with alcoholic cirrhosis admitted to the Internal Diseases Department with Dialysis Ward in the hospital in Wolomin between 2002 and 2004 year. Patients were divided into 3 groups according to renal disfunction: patients with HRS-1, patients with HRS-2 and patients with cirrhosis without renal failure. Each diagnosis was established basing on criteria of International Ascites Club. Different factors, which may influence a development of HRS, such as large--volume paracentesis without plasma expansion, bacterial infections, gastrointestinal bleeding and nephrotoxic drugs were analysed. Patients were treated with terlipressin and intravenous albumin infusions, antibiotics, diuretics, dopamine, haemodialysis and paracentesis. 10 patients (3 with HRS-1.5 with HRS-2 and 2 without renal failure) died, which is 15.4% of the all group. The mortality in the group of patients with HRS is high but complex treatment may be effective. Nowadays liver transplantation is the most effective method.

[Circadian profile of the prolactin concentration in the patients with end-stage renal failure]. / Dobowy profil stezen prolaktyny u chorych na schylkowa niewydolnosc nerek.

UNLABELLED: Determination of circadian of prolactine (PRL) profile and its relationship to selected clinical and laboratory indices in end-stage renal disease (ESRD) patients undergoing hemodialysis, peritoneal dialysis as well as those in predialysis period was the aim of the study. Investigations were carried out in 38 patients with ESRD aged 36 to 79 yr. (medium 59 +/- 11 yr.), (20 male, 18 female, 7 treated with peritoneal dialysis, 25 undergoing hemodialysis, 6 in predialysis period) and the control group consisting of 7 healthy volunteers (4 male and 3 female). Serum concentration of PRL was evaluated at 3:00, 7:00, 12:00, 18:00, 22:00. The influence of different dialysis methods, blood concentration of parathormone, hemoglobin, total protein, erytropoietin (EPO), C-reactive protein, EPO therapy and duration of dialysis therapy on the PRL profile was analyzed. Results were analyzed according to medium obtained values of daily PRL profiles and individual indexes of variation of the daily concentration. Impaired circadian PRL profile was found in the all of followed groups comparing to the control, which was based on flatting of the curve and decreasing of the nightly pick of secretion PRL. None of analyzed factors had normalized the PRL profile curve. CONCLUSIONS: The PRL profile in ESRD patients treated with hemodialysis, peritoneal dialysis and in predialysis period is changed. The PRL profile curve is flatted and there was no night pick of PRL secretion in the patients. PRL level was shown to increase with progress of the disease, and the highest levels were in hemodialysed patients. EPO treatment, general appearance improvement, increased hemoglobin level and any of studied different dialysis method did not normalize the altered PRL profile.

[Metoclopramide test in the patients with hyperprolactinemia due to end-stage renal failure]. / Test z metoklopramidem u chorych z hiperprolaktynemia w przebiegu schylkowej niewydolnosci nerek.

UNLABELLED: Evaluation of metoclopramide (MTC) test values in end-stage renal disease patients undergoing hemodialysis with different level of hyperprolactinemia was aim of the study. Clinical value of application of the MTC test and influence of different laboratory and clinical factors including erytropoietin treatment were examined. Sixty-eight hemodialysed patients (31 male and 37 female) aged 20-74 yr. (medium 48 +/- 13 yr.) underwent the MTC test, the control group consisted of 8 healthy volunteers (4 male and 4 female). 10mg of MTC was given i.v. and serum level of PRL was determined in 0, 30 and 60 min. after injection. Significant suppression of PRL stimulation in the patients was shown as compared with the controls after 30 min and delayed decrease of the curve values was found. An increase in the PRL level after 60 min in investigated group was lower than in control. Lower relative enhance of PRL level in 30 min was found and slower decrease after 60 min. Despite the slower decrease PRL level was lower in the patients than in the controls after 60 min. The highest relative increase in PRL level after 30 min was observed in the patients with lowest initial level of PRL (r=-0.471; p<0.001). Erytropoietin administration improved the response in the test (p=0.005) without relationship to the duration of erytropoietin treatment. There was influence of hemoglobin level on the results of the test. CONCLUSIONS: Results of the MTC test in end-stage renal disease patients is inadequate and the PRL response is diminished. Diagnostic value of the test in end-stage renal disease patients is low. Erytropoietin administration improves although not to the normal values the results of the MTC test.

[Hepatorenal syndrome. Cases report]. / Zespól watrobowo-nerkowy. Opis przypadków.

The hepatorenal syndrome is defined as renal failure in patients with severe liver disease. It may be diagnosed by exclusion of other potential factors which may cause renal failure, such as hypovolaemia, nephrotoxic drugs and severe bacterial infection. Liver transplantation is the target treatment leading to recovery of renal function. Other methods such as vasoconstrictors, renal replacement therapy and repeated paracenthesis with intravenous albumin infusions are also presented.