Longin Niemczyk

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 testosterone 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/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 parameters 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 testosterone 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.

Value of multilocus genetic risk score for atrial fibrillation in end-stage kidney disease patients in a Polish population

Genetic factors play a key role in the pathogenesis of atrial fibrillation (AF). We would like to establish an association between previously described single-nucleotide polymorphisms (SNPs) and AF in haemodialysed patients with end-stage kidney disease (ESKD-HD) as well as to assess the cumulative effect of all genotyped SNPs on AF risk. Sixteen SNPs were genotyped in 113 patients with AF-ESKD-HD and in 157 controls: without AF (NAF) and with ESKD-HD. The distribution of the risk alleles was compared in both groups and between different sub-phenotypes. The multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. Several loci showed a trend toward an association with permanent AF (perm-AF): CAV1, Cx40 and PITX2. However, GRS was significantly higher in the AF and perm-AF groups, as compared to NAF. Three of the tested variables were independently associated with AF: male sex, history of myocardial infarction (MI) and GRS. The GRS, which combined 13 previously described SNPs, showed a significant and independent association with AF in a Polish population of patients with ESKD-HD and concomitant AF. Further studies on larger groups of patients are needed to confirm the associations.

Copeptin Blood Content as a Diagnostic Marker of Chronic Kidney Disease

Plasma content of copeptin increases with the advancement of chronic kidney disease (CKD). The purpose of this study was to evaluate copeptin content as a potential marker of CKD, as a single pathology or with coexisting heart failure. Seventy-six patients were divided into the following groups: Group 1 (control), without CKD and heart failure; Group 2, CKD stage 3a; Group 3, CKD stage 3b; Group 4, CKD stage 4; Group 5, CKD stage 5; and Group 6, CKD stage 3b and heart failure. For all patients, plasma concentrations of copeptin, creatinine, urea, cystatin C, sodium, C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and blood pH were assessed. We found that plasma content of creatinine, urea, CRP, cystatin, NT-proBNP, and copeptin increased with CKD progression. Heart failure in CKD patients was not the cause of an appreciable increase of copeptin level. Copeptin/creatinine, copeptin/cystatin C ratios, and especially copeptin/eGFR ratio enhanced copeptin prognostic sensitivity concerning renal failure in CKD, compared with copeptin alone. The copeptin×NT-proBNP ratio decreased along CKD progression, reaching a nadir in the accompanying heart failure. In contradistinction, copeptin×NT-proBNP/creatinine ratio increased along CKD progression, reaching a peak in the accompanying heart failure. We conclude that copeptin is an important marker in CKD, but not so concerning heart failure in the disease. A decrease in copeptin×NT-proBNP and an increase in copeptin×NT-proBNP/creatinine ratio are useful markers of cardiac function decline in CKD.

Kidney dysfunction after hematopoietic cell transplantation—Etiology, management, and perspectives

Kidney dysfunction is a common complication of hematopoietic cell transplantation (HCT) with proven negative impact on early and long-term mortality. Causes of this complication are diverse, usually overlapping, and poorly understood. Therefore, management implicates multidirectional investigations and simultaneous treatment of suspected causes. The etiology is frequently unconfirmed due to a lack of specific markers and prevalence of contraindications to renal biopsy among HCT recipients. Herein, we provide a summary of etiology and propose an algorithm for evaluation of kidney injury after HCT. We also map out the most urgent areas for research that aim to identify patients at risk of severe renal injury and develop nephroprotective strategies.

Effect of Chronic Kidney Disease on Changes in Vasopressin System Expression in the Kidney Cortex in Rats with Nephrectomy

It is believed that the vasopressinergic system plays an important role in the pathogenesis of chronic kidney disease (CKD). The aim of this study was to evaluate the effect of CKD on changes in vasopressin system expression in the kidney cortex in rats with nephrectomy. The study was performed on 4 groups of Sprague Dawley (SPRD) rats: a control group (CN), 1/2 nephrectomy (N1/2), 2/3 nephrectomy (N2/3), and 5/6 nephrectomy (N5/6). Blood and the kidney cortex were collected to evaluate plasma copeptin concentrations and mRNA expressions of V1a vasopressin receptors (V1aR) and V2 vasopressin receptors (V2R) and V1aR, V2R, and aquaporin 2 (AQP2) protein levels. V1aR and V2R mRNA expression in the kidney cortex was significantly lower in the CN group compared with the other groups. In contrast, the V1aR, V2R, and AQP2 protein levels were significantly higher in the CN group compared with all of the nephrectomized groups. Plasma copeptin concentration was significantly lower in the CN group than in the nephrectomized groups. CKD caused significant changes in the expression of the vasopressinergic system. Further research is needed to explain the mechanisms of the impact of the vasopressinergic system on the kidney in CKD.

MULTIPLE INTERCOSTAL NEUROFIBROMAS IN A PATIENT WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

In a 55-year-old smoking man with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney disease (ADPKD), computed tomography of the chest was performed due to chronic cough. Multiple oval tumours (largest 32 mm ¥ 15 mm ¥ 12 mm) connected to intercostal nerves were noticed. There was no pleural infiltration or bone destruction. No symptoms or signs were reported. The changes were verified by magnetic resonance imaging as intercostal neurofibromas (Fig. 1). The patient underwent examinations for other features of neurofibromatosis 1 (NF1). However, he ultimately did not met the diagnostic criteria, and NF1 was excluded. The case is interesting, as coexistence of NF1 and ADPKD may impact patient’s outcome and management. Although intercostal neurofibroma may be observed in an individual without NF1, the presence of intercostal neurofibromas might be the first sign of NF1. Coexistence of NF1 and ADPKD is a very rare phenomenon. The awareness of the NF1 diagnosis in ESRD patients may be significant, as NF1 is a risk factor for neoplastic diseases. Renal transplantation, which should be considered, is also connected to increased risk of malignancy. Therefore, in the case of transplantation in a patient with NF1, he/she should undergo careful oncological screening. Additionally, including sirolimus into the immunosuppressive regimen should be considered due to its antineoplastic properties, and due to its influence on native polycystic kidneys and polycystic liver. The diagnostic criteria for NF1 include at least two of the following features: (i) six or more café-au-lait spots; (ii) two or more neurofibromas of any type or at least one plexiform neurofibroma; (iii) freckling in the axilla or groin; (iv) optic glioma; (v) two or more Lisch nodules of the iris; (vi) dysplasia of the sphenoid bone or the thinning of the long bone cortex; and (vii) first-degree relative with NF1. Ultimately, none of these features except neurofibromas were observed in our case. To our knowledge, there are no data in the published work concerning the risk of malignancy in individuals with isolated neurofibromas. Coexistence of NF1 and ADPKD, although rare, influences the patient management and should not be omitted. In patients with ADPKD and intercostal neurofibromas, evaluation for NF1 must be performed.