Real world analysis of high-cut-off (HCO) hemodialysis with bortezomib-based backbone therapy in patients with multiple myeloma and acute kidney injury.

BACKGROUND: In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. METHODS: Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. RESULTS: The median number of HCO hemodialysis sessions was 11 (range 1-42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. CONCLUSION: The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.

Factors responsible for cerebral hypoxia in hemodialysis population.

Brain tissue oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p?0.001) and higher BNP level (r=-0.45, p=0.01). The rSO(2) value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO(2) values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO(2) in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.

Treatment of early diagnosed HCV infection in hemodialyzed patients with interferon-alpha. Treatment of hepatitis C.

BACKGROUND: Acute and early diagnosed hepatitis C virus (HCV) infections are rare diagnoses. Patients on regular dialysis treatment (RDT) are at risk of acquiring HCV infection. AIMS OF THE STUDY: (1) To determine the efficacy and safety of two-phase induction treatment of acute and early diagnosed HCV infections in patients on RDT, and (2) to establish the importance of serum HCV RNA testing at defined time points of treatment for the prediction of the therapeutic effect. THERAPEUTIC PROTOCOL: Antiviral treatment consisted of two different phases: phase A therapy was interferon (IFN)-alpha 2b 10 million units (MU) s.c. administered daily for 21 days followed by phase B with IFN-alpha 2b 3 MU s.c. administered 3 times weekly for 12 weeks. RESULTS: (1) Efficacy of the treatment: A sustained virological response (SVR) was achieved in a total of 13/18 patients (72%). SAFETY: We did not observe any serious side effects of the treatment. The most pronounced side effect was the myelosuppression caused by IFN-alpha. (2) SVR prediction: Patients with negative serum HCV RNA at day 6 achieve SVR more frequently than those with positive HCV RNA at day 6 (p = 0.074). CONCLUSIONS: Treatment of acute and early diagnosed HCV infections in hemodialyzed patients is much more effective than treatment of chronic infection. Even relatively high doses of IFN at the beginning of therapy (10 MU daily) are tolerated well by the patients.

Pregnancy-associated plasma protein A during hemodialysis with polyamide and diacetate cellulosic membranes.

Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic factor of acute coronary syndrome in the general population. It is elevated in hemodialysis (HD) patients and at baseline, it was shown to be related to inflammation and oxidative stress. The aim of the study was to examine the relationship of PAPP-A and oxidative stress and inflammatory markers to HD treatment. Studied parameters were determined in 10 chronic HD patients treated with low flux polyamide (1st session) and diacetate cellulosic membranes (2nd session) at the beginning, after 15 minutes and at the end of the dialysis session. TRACE method (Time Resolved Amplified Cryptate Emission) was used for PAPP-A assessment. Results were evaluated with ANOVA. PAPP-A levels did not depend on the type of HD membrane but changed significantly with the time of the HD session. They increased significantly from the beginning of HD to 15 min and then decreased to the end of the HD session - p<0.05 15 min of HD vs start, p<0.01 end vs start, p<0.0001 end vs 15 min of HD for polyamide membrane and p=0.05 15 min of HD vs start, p<0.01 end vs start, p<0.0001 end vs 15 min of HD for diacetate cellulosic membrane. Changes in other parameters and differences between membranes were only minimal. We can conclude that PAPP-A as a marker of cardiovascular damage shows significant changes during the HD session. Its initial increase might be ascribed to its release from complexes or storage. During dialysis, it might be destroyed or cleaved and removed as free fragments. Its levels both before and after the HD session are higher than in healthy subjects.

[Mediators of amyloidogenesis and cytokines in dialysis-related amyloidosis]. / Mediátory amyloidogeneze a nekteré cytokiny u dialyzacní amyloidózy.

BACKGROUND: Dialysis related amyloidosis (DRA) is a severe complication of the long-term dialysis treatment. beta 2 microglobulin and probably other factors influence the development of amyloid deposits. We investigated some of these factors during hemodialysis session. METHODS AND RESULTS: We investigated 20 patients undergoing regular hemodialysis treatment. Patients were divided into AMYL group (with histologically proven DRA) and NE-AMYL group (without signs of DRA). Plasma levels of following factors were investigated using standard ELISA kits: serum amyloid A (SAA), interleukin-6 (IL-6), macrophage-colony stimulating factor (M-CSF). In addition plasma concentrations of C-reactive protein (CRP) and beta 2 microglobulin (beta 2M) were investigated in the AMYL group. All these parameters were studied during different time periods of the hemodialysis session. Plasma levels of SAA and IL-6 did not increase during hemodialysis session and we did not find any difference in plasma levels of these factors between the group of patients with AMYLand NE-AMYL. Plasma levels of M-CSF increased during hemodialysis and its levels in AMYL group were significantly higher in comparison with NE-AMYL group at the end of hemodialysis session (5345.10 +/- 340.42 vs. 3458.45 +/- 332.15 pg/ml, p = 0.0011). A linear correlation was found between plasma levels of SAA and CRP during hemodialysis whereas no correlation was found between plasma levels of beta 2M and other factors. CONCLUSIONS: Our study suggests that plasma levels of M-CSF are increased in patients with chronic renal failure. Significant increase of M-CSF levels in the AMYL group could lead to greater activation of monocyte-macrophage system and could serve as factor supporting amyloid deposition process.

Advanced glycation end products and advanced oxidation protein products in hemodialyzed patients.

Chronic renal failure is associated with increased oxidative and carbonyl stresses that contribute to long-term uremic complications. In our study, we determined two markers of these stresses--AGEs (advanced glycation end products) and AOPP (advanced oxidation protein products)--in chronic hemodialysis patients in order to find out their relationship to the dialysis treatment. Plasmas of 20 hemodialyzed patients treated with modified cellulose membranes were examined at 0 and 15 min and at the end (i.e. after 4 h) of the dialysis session. AGEs were estimated using a spectrofluorometric method (excitation 350 nm, emission 440 nm) and are expressed in AU (arbitrary units)/g protein. AOPP were determined spectrophotometrically (absorbance at 340 nm) and are expressed in chloramine units per gram of protein (micromol/g). AOPP decrease slightly from 0 to 15 min of the dialysis procedure (4.0 +/- 1.5 vs. 3.0 +/- 0.9 micromol/g, p < 0.01). However, they are increased at the end of the session (5.0 +/- 2.1 micromol/l vs. 15 min, p < 0.01, not significant vs. beginning). On the other hand, AGEs decrease continuously from the beginning to the end of the session (mainly in the first minutes of the dialysis) (1.52 +/- 0.34 x 10(4) AU/g at 0 min, 1.39 +/- 0.33 x 10(4) AU/g at 15 min, p < 0.001 vs. beginning, 1.30 +/- 0.33 x 10(4) AU/g at the end, p < 0.001 vs. beginning, not significant vs. 15 min). Neither AGEs nor AOPP correlate with the age of hemodialyzed patients and with the number of years of the dialysis treatment. AOPP correlate with AGEs before the dialysis session (r = 0.62, p < 0.05) but not after the session (r = 0.29, not significant). According to our results, AGEs may serve more as a marker of chronic damage while AOPP may better describe acute oxidative stress during the dialysis treatment.

[Sleep disorders in hemodialysis patients]. / Poruchy spánku u hemodialyzovaných pacientu.

BACKGROUND: Many hemodialyzed patients complain about bad sleep. The aim of this study was to learn the subjective view of patients on their sleep and its influence by hemodialysis treatment. METHODS AND RESULTS: A simple questionnary containing 20 questions concerning sleep was prepared and given to regularly hemodialyzed patients in two hemodialysis centres. Uncorperating as well as severely ill patients were excluded. The questionnary was responded by 103 patients (mean age 60.4 years)--61 men (mean age 56.7 years) and 42 women (mean age 65.7 years). 34% of patient regard their sleep as bad. 45.6% of dialyzed patients feel restlessness of legs during the night and 32% snore or have some breath problems. 38% of patients considered their sleep as better before starting the hemodialysis treatment, in 14.6% the sleep became better after starting the dialysis treatment. CONCLUSIONS: Sleep disorders in hemodialysed patients worsen the quality of life of these patients. Moreover, sleep disorders represent a serious problem as they can increase the mortality.

[Dialysis therapy in the Czech Republic in 1999]. / Prehled o dialyzacní lécbe v Ceské republice v roce 1999.

Number of HDS patients has stabilised; however, the technical background of the haemodialysation program is not sufficient, 40% of the dialysation monitors has been amortised. In the dialysed population numbers of elderly patients (60%) and diabetics (33%) rise, thus rise the number of polymorbid patients and about 1/3 of new patients come form "the street". Not surprisingly it brings high mortality (20%). Six per cent of patients were treated with peritoneal dialysis in 1999, the highest number achieved in the present history of this method. This trend should be kept in future.

[Dialysis therapy in the Czech Republic in 1998 and in the future]. / Dialyzacní lécba v Ceské republice v roce 1998 a v budoucnosti.

1. The number of dialyzation centers has not changed during the past two years. Their steep increase occurred in 1990-1995. This development made this treatment available without former limitations (on account of diagnosis and age). 2. In the dialyzed population during the last five years the number of patients in more advanced age groups is increasing. More than half the patients are older than 60 years. During this period there was a marked increase of diabetic subjects and in 1997 they accounted already for one third of the dialyzed population. 3. In the number of patients treated by haemodialysis we still lag behind the countries of the EU. An adverse indicator of the quality of treatment is the high mortality rate. 4. It is essential to ensure early dispensarization of patients with a creatinine level above 300 mumol/l in the predialyzation ambulatory department. 5. Only a very small percentage of patients is treated by peritoneal dialysis as this is not a traditional method in this country.

[Dialysis therapy in the Czech Republic in 1995]. / Dialyzacní lécba v Ceské republice v roce 1995.

1. The number of haemodialyzation centres has more than doubled in the course of five years which increased the dialyzation capacity and at present no patient in the Czech Republic should be denied dialyzation treatment on technical or financial grounds. 2. The number of newly enlisted patients "from the street" remains unfavourable, one third, who are not prepared for this financially pretentious treatment and who have many complications. General practitioners and diabetologists should refer in time patients with chronic renal failure (with a creatinine level above 300 mumol/l) to nephrological--predialyzation clinics. 3. The dialyzed population is aging and in the dialyzation programme polymorbid patients, specially diabetics are increasing in numbers. Therefore the mortality has a rising trend and this will persist. The most frequent cause of death are, similarly as in other countries, cardiovascular complications. 4. The development of another method for the treatment of renal failure is promising--peritoneal dialysis which is used in treatment of almost 5% patients. 5. The number of patients treated by HD per 1 million population is relatively high but only because other therapeutic methods applied in renal failure are not used in a sufficient number of patients. This results in a lower rate of patients treated by RRT methods (HD+PD+TPL)/1 million population, as compared with advanced European countries.

[Changes in the conjunctiva and cornea in dialyzed patients]. / Zmeny spojivky a rohovky u dialyzovaných nemocných.

The author examined 119 patients having regular dialyzation treatment and a control group of 90 healthy subjects, divided into groups by decades. Depending on the intensity of pathological changes, they created four categories; the fifth comprised normal findings. The prepared from the bioptic material of the conjunctiva of two patients preparations which were examined for calcium and amyloid deposits. Pathological changes were found in 74.8%. The authors try to explain the cause of conjunctival and corneal changes, consistent with the theory of hastened ageing in chronic renal failure of patients treated by regular haemodialysis. The so far unique findings of amyloid of the conjunctiva could be possibly used in future for the diagnosis of amyloidosis instead biopsies.

[Erythropoietin in the treatment of anemias]. / Pouzití erytropoetinu v lécbe anémií.

Recombinant erythropoietin (r-HuEPO) was the first growth factor introduced into clinical practice. The main indication for its therapeutic use remains treatment of anaemias during chronic renal failure. In Czech Republic it is at present administered to 55% of patients included in a regular haemodialyzation program and in the pre-dialyzation stage of the disease, consistent with European practice. In addition to a marked improvement of the quality of life, during r-HuEPO treatment also the prevalence of some cardiovascular complications is reduced and immune functions improve. The list of diseases where r-HuEPO therapy is indicated has been, however, extended nowadays. A very favourable effect was recorded in some haematological malignicies and solid tumours. The best results were observed so far in the treatment of anaemia associated with multiple myeloma and chronic lymphatic leukaemia, and also in malignant lymphomas, carcinoma of the breast and ovary. It is used also in the treatment of suppressed erythropoiesis resulting from cytoreducing therapy. Other indications include anaemia after transplantations of bone marrow, preparation before autologous transfusions and some cases of myelodysplastic syndrome. The authors mention also other contemporary possibilities of r-HuEPO use.

[Dialysis therapy in the Czech Republic in 1994]. / Dialyzacní lécba v Ceské republice v roce 1994.

1. In 1994 were 81 haemodialysis centers in the Czech Republic (including 12 private ones, i.e. 7.7 p.m.p.). 2. The capacity of dialysis centres enabled an outstanding number of new patients to be accepted--120 p.m.p. (the European average was half that number). Majority of the new patients were from higher age groups and diabetics. The number of patients, who were not followed prior to renal replacement therapy, still remains one third of the newly accepted ones. 3. In 1994 there were 3592 patients on dialysis treatment--342 p.m.p. (the maximum number so far), but by December 31st 1994 there were 2691 patients--256 p.m.p. surviving on dialysis treatment. We have achieved higher number dialysed patients p.m.p. than any other country of the former Eastern bloc, including the GDR. Mortality was 14%. 4. Hepatitis B as well as C remains a major problem, although there has been a slight decline of HBsAg positive patients. 5. The technical facilities for dialysis treatment are not optimal. 6. A favourable trend continued in the development of peritoneal dialysis programme.

[Dialysis therapy in the Czech Republic in 1993]. / Dialyzacní lécba v Ceské republice v roce 1993.

1. The number of haemodialyzation centres increased in 1993 to 6.6/1 million population and thus also the number of dialyzation beds increased to 47.1/1 million population. 2. The extended and free dialyzation capacity made it possible to cover a record number of new patients (96/1 million population as compared with the European average of 61/1 million population). However, the number of older age groups and diabetics increased (in the group above 50 years of age to 17%). The number of patients admitted "from the street" did not decline--it still accounts for one third! 3. In the course of 1993 277 patients/1 million population were dialyzed which is more than in all states of the former eastern bloc. To the date of Dec. 31, 1993 215 patients/1 million population survived. The mortality rate was 13.2%. 4. Hepatitis still remains a major problem--the number of HbsAg positive patients during the last three years did not change, similarly as the prevalence of hepatitis. 5. The dialyzed population is steadily getting older which is not favourable for its prosperity (62% of the patients are older than 50 years). 6. Technical equipment for dialyzation treatment is not yet optimal--21% of the apparatus was amortized, bicarbonate dialysis in all patients was used only in half the centres. 7. The favourable trend in the development of peritoneal dialysis (CAPD) continued, a threefold number of patients was treated as compared with 1992.

[Rapidly progressive glomerulonephritis in a solitary kidney positive for anti-glomerular basement membrane antibodies and antineutrophil cytoplasmic antibodies]. / Rychle progredující glomerulonefritida v solitární ledvine s pozitivními protilátkami proti bazální membráne glomerulu (AGBMA) a protilátkami proti cytoplazme neutrofilních leukocytu (ANCA).

The authors describe the case-report of a 72-year-old female patient with acute failure of a solitary kidney with complete functional breakdown which developed within several days and was due to rapidly progressive glomerulonephritis (RPGN) with concurrent positivity of antineutrophil cytoplasmatic autoantibodies (ANCA) and anti-glomerular basement antibodies (AGBMA). Intensive combined immunosuppressive therapy with methyl prednisolone, cyclophosphamide and azathioprine and concurrent plasmaphereses led to negativity of both types of antibodies but were not able to restore sufficient renal function and regular dialysis treatment to be started. Subsequently AGBMA remained negative, while ANCA became again positive. Despite this partial restoration of renal function was manifested by an increased diuresis and the frequency of dialyses could be reduced. The case-report has several remarkable features. An uncommon RPGN of the antirenal type is involved, moreover in a solitary kidney with concurrent C-ANCA positivity. The concurrent presence of ANCA and AGBMA autoantibodies in RPGN has been described in the literature only in several tens of cases. So far it was not described in our country. Based on their experience the authors conclude: 1. a solitary kidney cannot be considered in case of suspected RPGN as a strict contraindicatio of renal biopsy, 2. RPGN with concurrent positivity of ANCA and AGBMA is indicated for long-term immunosuppressive therapy on account of a more favourable prognosis than simple antirenal RPGN, and also with regard to a possible suspected systematic vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Iron stores in patients with chronic kidney failure treated with recombinant human erythropoietin]. / Sledování zásob zeleza u nemocných s chronickým selháním ledvin lécených rekombinantním lidským erytropoetinem.

Nine patients with anemia of chronic renal failure were treated with recombinant human erythropoietin (rHuEPO) in dose 50-150 IU/kg/week. After 8 weeks the treatment was maintained with 30-50 IU/kg/week for one year. A significant increase of hemoglobin (Hb) level and red blood cell (RBC) count was observed in all patients. Administration of rHUEPO maintained Hb level higher than 100 milligrams and RBC count above 3.0 x 10(12)/l. Iron stores decreased in all patients. Parameters reflecting either the real amount of iron available for erythropoiesis or iron stores in erythroid precursors, i.e. red cell ferritin (eF), free erythrocyte protoporphyrin (FEP) and transferrin saturation (satTRF) were the most reliable tools for diagnosis of iron deficient erythropoiesis. Serum ferritin (sF) was not decreased in most patients, however, sF level was below 50 micrograms/l in all patients at the time of diagnosis of iron deficiency. Iron supplementation in a daily dose allowing absorption of 100mg of elementary iron was sufficient to cover the increased demand for iron in rHuEPO treated patients.

[Rhabdomyolysis and acute renal failure]. / Rabdomyolýza a akutní renální selhání.

Rhabdomyolysis is damage of the skeletal muscles due to different causes which leads to the release of the contents of muscle cells into the blood stream and conversely to the penetration of water and other substances into muscles via the damaged membrane. This initiates many processes which damage the organism: hypovolaemia, hypocalcaemia, hyperkalaemia, hyperuricaemia, disseminated intravascular coagulation, renal failure. Renal failure in particular is a frequent and very serious complication. However, when correct treatment is provided, it is usually reversible. The diagnosis and differential diagnosis is not difficult if the possible presence of rhabdomyolysis is considered. Therapy involves in particular supplementation of the vascular volume and forced diuresis.

[Acute kidney failure associated with rhabdomyolysis]. / Akutní selhání ledvin na podklade rabdomyolýzy.

The authors describe three cases of rhabdomyolysis and acute renal failure. In all patients rhabdomyolysis developed in conjunction with ingestion of alcohol, in two moreover in combination with compression of an extremity by body weight during prolonged immobility. One patient was hospitalized on the day when rhabdomyolysis developed, the second one more than 24 hours after and the third one only several days after development of the condition. In none of them the diagnosis was established before the development of renal failure. All were subjected repeatedly to haemodialysis. One patient died from a complication--embolism of the brain--the remaining two patients recovered without sequelae. In the discussion the authors deal with reasons of late diagnosis of the disease.

[Dialysis therapy in the Czech Republic in 1991]. / Dialyzacní lécba v Ceské republice v roce 1991.

In the Czech Republic in 1991 2064 patients with chronic renal failure were treated in 43 haemodialysation centres. The number of newly enlisted patients was high--655 patients. Despite this the mean number of 196.5 patients/1 million population is lower than the European average. Fear of doctors is aroused by inadequate technical equipment and the lagging replacement of amortized equipment. The age of dialyzed patients is rising, the number of polymorbid patients and diabetics is increasing. It can be assumed that the mortality will increase and the number of transplantable patients will decline. A high incidence of hepatitis still persists. The most frequent cause of acute renal failure are complications after surgery. Acute haemodialysis on account of intoxication was made most frequently after intoxications with drugs.