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.

Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress.

BACKGROUND: Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS. SUMMARY: Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and - in high-risk cases - considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted.

Renal Involvement in Systemic Sclerosis: An Update.

BACKGROUND: Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. SUMMARY: Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and life-threatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients' outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.

[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.

Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group.

INTRODUCTION: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. AIMS: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. PATIENTS AND METHODS: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. RESULTS: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. CONCLUSIONS: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS.

Stem cell mobilization in patients with dialysis-dependent multiple myeloma: Report of the Polish Myeloma Study Group.

INTRODUCTION: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. MATERIALS AND METHODS: Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Myeloma Study Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. RESULTS AND CONCLUSIONS: The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 106 cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 106 cells/kg) - was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m2 ) and cyclophosphamide (> 2 g/m2 ) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.

[Current approaches in the treatment of hyperphosphatemia in chronic kidney disease].

Hyperphosphatemia is a common finding in advanced chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Optimal phosphate control in dialysis patients is a real challenge. In the article, the authors discuss the main phosphate-lowering approaches, such as a change of dietary habits with phosphate restriction and pharmacologic treatment. Several old and new currently available oral phosphate binders are reviewed with their advantages and disadvantages.

[MGRS - monoclonal gammopathy of renal significance].

MGRS represents a group of kidney disorders caused by monoclonal gammapathy that is secreted by B cell or plasma cell clone. Kidney biopsy is required in the diagnosis, in the treatment - chemotherapy. When the hematology remision is reached, kidney remision is possible. In case of end-stage kidney disease despite hematologic remission - kidney transplantation may be considered.

[Spectrum of monoclonal gammopathies].

The monoclonal gammopathies are defined as heterogenous group of diseases characterized by proliferation of a single clone of plasma cells, producing immunoglobulin or light (rarely heavy) chains, which can be detected in blood or urine as monoclonal (M) protein. The most common among them is monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic benign disorder, present in ~ 3% of the population aged ≥50 years. However MGUS is a pre malignant condition and may progress to symptomatic multiple myeloma or related malignancies, with annual rate of approximately 1%. The clone may also produce kidney damage, resulting from just the protein M, with different patterns of renal disease. Since the lesions are progressive and may be severe leading to a significant morbidity the term "monoclonal gammopathy of renal significance (MGRS)" has been recently introduced.

[Systemic lupus erythematosus - news 2017].

Systemic lupus erythematosus is a chronic autoimmune disease with diverse manifestations and clinical course, required multidisciplinary treatment. The etiology, pathogenesis and optimal treatment are still unknown. There are two summaries on SLE, published in 2017, presented below.

[Approach to recurrent urinary tract infections in women].

Recurrent urinary tract infections (rUTI), defined as ≥3 UTI/year or ≥2 UTI/half year, are among the most frequent bacterial infections in women and pose a significant clinical challenge to general practitioner. The main risk factors are: sexual activity with different partners, and - in postmenopausal women - urinary incontinence or incomplete voiding. In the article the current treatment and prevention strategies for rUTI are discussed.

[Kidney disease in HIV-infected patient].

In the developed countries with an access to highly active antiretroviral therapy (HAART), the spectrum of renal complications observed in patients infected with HIV has shifted from HIV-associated kidney diseases to medications-related nephrotoxicities. In this article all types of these disorders, ranging from HIV-associated nephropathy (HIVAN), immune mediated glomerulopathies (HIVICK), and thrombotic microangiopathies to induced by HAART tubulopathies, acute toxic tubular necrosis, acute interstitial nephritis, crystal nephropathy, and chronic kidney disease have are shortly reviewed.

[Advances in the management of renal cell carcinoma].

Renal cell carcinoma accounts for about 3-4% of all malignancies and its incidence is steadily rising. The article presents in short the rationale behind the targeted therapies and provides an update on current therapeutic approaches to metastatic renal cell carcinoma. It also summarizes the most recent developments in the immunotherapy such as immune checkpoint inhibitors, anti-cancer vaccines and chimeric antigen receptors on T cells.

[Paricalcitol - a selective vitamin D receptor activator for secondary hyperparathyroidism in patients with chronic kidney disease].

Secondary hyperparathyroidism is a frequently encountered complication of chronic kidney disease (CKD) attributable to altered phosphate/calcium homeostasis, increased synthesis of phosphaturic hormone (FGF-23) and profound active vitamin D deficiency. The disorder is associated with severe bone disease, progressive cardiovascular calcification and increased mortality. Calctriol and its analogs (alphacalcidol) can suppress parathyroid activity, however at the cost of hypercalcemia and hiperphosphatemia, thus aggravating the vascular disease. During the last decade, selective vitamin D receptor activators (VDRA) have been introduced, that reduce parathyroid activity with minimal changes in calcium and phosphate metabolism. Paricalcitol is the only selective VDRA registered in Europe for the management of patients with different stadia of CKD. For today, with its efficacy and safety confirmed in several clinical trials paricalcitol increases the vitamin D therapeutic window in this population. Furthermore, the clinical data on its possible positive effect on survival together with its reduced or even lacking experimental procalcifying effects on vessels, call for extensive research, since selective VDRA may provide additional clinical benefits going beyond mineral-bone disorder.

Smaller caliber renal arteries are a novel feature of uromodulin-associated kidney disease.

Hyperuricemia is very common in industrialized countries and known to promote vascular smooth muscle cell proliferation. Juvenile hyperuricemia is a hallmark of uromodulin-associated kidney disease characterized by progressive interstitial renal fibrosis leading to end-stage renal disease within decades. Here we describe a member of a Polish-German family with a history of familial background of chronic kidney disease, hyperuricemia, and gout. This patient had hypertension because of bilateral small renal arteries, hyperuricemia, and chronic kidney disease. Clinical and molecular studies were subsequently performed in 39 family members, which included a physical examination, Duplex ultrasound of the kidneys, laboratory tests for renal function, and urine analysis. In eight family members contrast-enhanced renal artery imaging by computed tomography-angiography or magnetic resonance imaging was conducted and showed that bilateral non-arteriosclerotic small caliber renal arteries were associated with hyperuricemia and chronic kidney disease. Of the 26 family members who underwent genotyping, 11 possessed the P236R mutation (c.707C>G) of the uromodulin gene. All family members with a small caliber renal artery carried the uromodulin P236R mutation. Statistical analysis showed a strong correlation between reduced renal artery lumen and decreased estimated glomerular filtration rate. Thus, bilateral small caliber renal arteries are a new clinical phenotype associated with an uromodulin mutation.

Is Free Testosterone Concentration a Prognostic Factor of Survival in Chronic Renal Failure (CRF)?

BACKGROUND: Lowered testosterone level in CRF patients is associated with elevated risk of death due to cardiovascular reasons, and is influenced by many factors, including acid-base balance disorders. AIMS: evaluation of testoste-rone concentration (TT) and free testosterone concentration (fT) in pre-dialysis and dialysis patients; assessment of TT and fT relationships with biochemical parameters; evaluation of prognostic importance of TT and fT in predicting patient survival. MATERIAL AND METHODS: 4 groups of men: 14 - on hemodialysis (HD), 13 - on peritoneal dialysis (PD), 9 - with chronic renal failure (CRF) and 8 - healthy (CG), aged 56±17, 53±15, 68±12, 43±10 years, respectively. TT and biochemical para-meters were measured; fT was calculated. RESULTS: The lowest TT and fT were observed in HD and CRF, the highest - in CG (p=0.035 for TT; p=0.007 for fT). fT in CRF and CG were different (p=0.031). TT and age was associated in HD (p=0.026). Age and fT was strongly associated in PD (p<0.001). After adjustment for age, TT was negatively associated with BMI (p=0.013) and fT was positively associated with HCO3 level (p=0.007). fT was lower in those who died during 5 years of observation than in survivors (p=0.009). We have found that, opposite to TT, fT appeared to be a better predictor of 5-year survival than age. After combining pH and HCO3 levels into a single variable - no acidosis, acidosis with HCO3 normal serum level, acidosis with low concentrations of HCO3 and adjustment for age and the study group - a trend toward the lowest values of free testosterone in decompensated acidosis was observed (ptrend=0.027). Such a trend was not seen for testosterone concentrations (ptrend=0.107). CONCLUSIONS: Total and free testosterone levels were lower in HD and pre-dialysis than in healthy patients. Free testost-erone level may predict long-term survival better than age. Total and free testosterone levels are lower in metabolic acidosis and total and free testosterone levels were positively associated with HCO3 level.

Visceral adipose tissue is associated with insulin resistance in hemodialyzed patients.

BACKGROUND: It has not been definitively established which factors affect insulin resistance (IR) and whether dialysis decreases IR. The aim of this study was to investigate factors that may have an influence on homeostasis model assessment (HOMA-IR) in hemodialyzed patients (HDpts) and to compare IR between HDpts and healthy subjects. MATERIAL AND METHODS: We examined 33 HDpts and paired 33 subjects of the control group, matched for sex, age, and BMI. We analyzed concentrations of insulin, glucose, leptin, resistin, and total and high-molecular-weight adiponectin (HMWad) in serum. Using computed tomography in HDpts, we evaluated visceral adipose tissue (VAT), concentrations of visfatin, CRP, and IL-6. RESULTS: HOMA-IR (median, 1.3 vs. 1.4, P=0.19), insulin (median 6.8 vs. 6.0 µIU/mL, P=0.7), glucose (79 mg/dL vs. 93 mg/dL, P=0.001). IR in HDpts is dependent on VAT (r=0.36, P=0.04) and this relationship is stronger than the relationship of BMI and IR (r=0.3, P=0.1). In HDpts we found higher concentrations of leptin (P=0.001) and resistin (P<0.001), with no relation to IR. HMWad and its percentage in relation to total adiponectin are higher in HDpts (P=0.03 and P<0.001, respectively). CONCLUSIONS: HOMA-IR in HDpts does not differ from the control group. In HDpts it depends on the quantity of VAT and this relationship is stronger than with BMI. In HDpts leptin and resistin do not influence IR. HMWad and its percentage in total adiponectin are significantly higher in HDpts.

[Renovascular hypertension]. / Nadcisnienie naczyniowo-nerkowe.

Renovascular hypertension (RVH) is one of the most common causes of secondary hypertension. In about 90% of cases it is due to atherosclerotic renal artery stenosis, often accompanied by severe occlusive disease in the other vessels, and as such carries a bad prognosis. In the remaining 10% patients (usually young women) the underlying vascular lesion is fibromuscular dysplasia. A presence of RVH should be suspected in patients with severe or resistant hypertension, sudden decline of renal function, sudden development or worsening of hypertension, flash pulmonary edema, impairment of renal function after treatment with renal-angiotensin-aldosterone system (RAAS) antagonists. Those patients should be screened with Doppler ultrasound, followed by computer tomography or magnetic resonance angiography. In most cases intensive and well-controlled medical treatment with RAAS blockers, aldosterone and/or calcium antagonists, with an addition of statins and platelet-inhibiting drugs is succesful. However in a selected cases renal revascularization may be necessary.