Trends in kidney transplantation rate across Europe: study from the ERA Registry.

BACKGROUND: The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. METHODS: The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. RESULTS: The total KT rate in the 40 participating countries increased with 1.9% annually  [95%  confidence  interval  (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). CONCLUSIONS: The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.

Cell proliferation and apoptosis in Wistar rat kidney after renal mass ablation and low-dose irradiation.

UNLABELLED: Cell proliferation and apoptosis in the remnant rat kidney after treatment with low-dose irradiation was investigated. MATERIAL AND METHODS: In the first group (n=9), adult male Wistar rats underwent 5/6 nephrectomy (NPX); in the second group (n=9), NPX was combined with low-dose irradiation. Rats without surgery and irradiation formed the control group (n=9). RESULTS: Hypertension and proteinuria induced by NPX were decreased by 3-Gy irradiation. The 5/6 NPX rats showed a dramatic increase in proliferating and apoptotic cells in the glomeruli and in the distal tubules at week 2, which was significantly decreased by low-dose irradiation. CONCLUSION: The data demonstrate that low-dose irradiation is a factor slowing the process of chronic renal injury.

Assessment of urea removal in haemodialysis and the impact of the European Best Practice Guidelines.

BACKGROUND: Dialysis adequacy, assessed by urea kinetics, is an important determinant of patient outcome, and is therefore an important clinical performance indicator. In this perspective, renal registry data may be useful to compare practices across countries. To serve that purpose available data should be comparable and preferably collected using a standardized procedure. The aim of this study, initiated by the European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) QUality European STudies (QUEST) initiative, was to make an inventory of the different methods used to determine urea kinetic measurements in the light of the European Best Practice Guidelines. METHODS: Via their national and regional registries, European haemodialysis centres were invited to complete a questionnaire regarding their practice of measuring dialysis adequacy. RESULTS: Fourteen regional or national registries among 51 sent back 255 questionnaires. Great variability in the methodology to assess Kt/V was observed. The urea reduction ratio (URR) was used alone by 37% (in association 46%) of dialysis centres, spKt/V by 25% (35%) and on-line clearance by 4% (12%), whereas only 10% (13%) used eKt/V, as recommended by EBPG. Forty percent of centres measured urea removal less than once a month, 6% of which never measured urea removal and 9% only every 6 months or less frequently. CONCLUSION: Despite the fact that the use of URR is not recommended by EBPG, it was the most commonly used indicator to measure urea removal, whereas eKt/V was only used by a small minority of centres. This study allowed us to point out the need to standardize definitions and procedures and to develop an effective plan for implementation of the guidelines.

Treatment diets in Estonian health care institutions.

New system and nomenclature of diets for Estonian health care institutions have been developed in the university hospital based on theoretical and practical experience obtained over several years of cooperation with medical scientists from different fields of specialization. The nomenclature of diets includes ordinary food and eight groups of diet food with subgroups. The normative values of the basic nutrients are in accordance with the Estonian and Nordic nutritional recommendations. The whole system includes the menus and recipes of nutritional food portions. The system of treatment diets helps to optimize proper nutrition in different departments and organize better patient care.

Resequencing PNMT in European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1.

BACKGROUND: Human linkage and animal QTL studies have indicated the contribution of genes on Chr17 into blood pressure regulation. One candidate gene is PNMT, coding for phenylethanolamine-N-methyltransferase, catalyzing the synthesis of epinephrine from norepinephrine. METHODS: Fine-scale variation of PNMT was screened by resequencing hypertensive (n = 50) and normotensive (n = 50) individuals from two European populations (Estonians and Czechs). The resulting polymorphism data were analyzed by statistical genetics methods using Genepop 3.4, PHASE 2.1 and DnaSP 4.0 software programs. In silico prediction of transcription factor binding sites for intron 1 was performed with MatInspector 2.2 software. RESULTS: PNMT was characterized by minimum variation and excess of rare SNPs in both normo- and hypertensive individuals. None of the SNPs showed significant differences in allelic frequencies among population samples, as well as between screened hypertensives and normotensives. In the joint case-control analysis of the Estonian and the Czech samples, hypertension patients had a significant excess of heterozygotes for two promoter region polymorphisms (SNP-184; SNP-390). The identified variation pattern of PNMT reflects the effect of purifying selection consistent with an important role of PNMT-synthesized epinephrine in the regulation of cardiovascular and metabolic functions, and as a CNS neurotransmitter. A striking feature is the lack of intronic variation. In silico analysis of PNMT intron 1 confirmed the presence of a human-specific putative Glucocorticoid Responsive Element (GRE), inserted by Alu-mediated transfer. Further analysis of intron 1 supported the possible existence of a full Glucocorticoid Responsive Unit (GRU) predicted to consist of multiple gene regulatory elements known to cooperate with GRE in driving transcription. The role of these elements in regulating PNMT expression patterns and thus determining the dynamics of the synthesis of epinephrine is still to be studied. CONCLUSION: We suggest that the differences in PNMT expression between normotensives and hypertensives are not determined by the polymorphisms in this gene, but rather by the interplay of gene expression regulators, which may vary among individuals. Understanding the determinants of PNMT expression may assist in developing PNMT inhibitors as potential novel therapeutics.

Morphological changes in experimental postischemic rat kidney. A pilot study.

The aim of our study was to investigate the changes in the early stages (at weeks 2 and 4) of experimental acute renal failure after short-time ischemia-reperfusion (I/R) compared with the impact of Losartan. Twenty male Wistar rats were divided into three groups: sham-operated rats (2 weeks), I/R groups (2 and 4 weeks); I/R and Losartan-treated groups (2 and 4 weeks). I/R was produced in adult rats by clamping the left kidney renal artery and renal vein for 40 min. The angiotensin II receptor antagonist Losartan was added to the drinking water (40 mg/l), and treatment was started on the first day after the I/R. Body weight, systolic blood pressure (SBP) and 24 h urine amount was measured every week. Urine amount and SBP was higher in I/R groups compared to sham-operated rats. Early stage acute renal disease was characterized by focal segmental glomerulosclerosis (FSGS) and interstitial fibrosis (IF) at weeks 2 and 4 after I/R. In the Losartan group, 2 weeks after the surgery, FSGS, IF and mesangial cell proliferation was decreased, but at week 4 these parameters showed a tendency to increase. Marked changes take place in tubular epithelial cells, especially in I/R groups. Angiotensin II receptor blocker AT1RA Losartan in the small dose (40 mg/l) had no effect on hypertension and urine excretion in the experimental I/R model. A pilot study revealed that tubular basement membrane thickness is markedly increased after I/R.

Low-dose radiation modifies the progression of chronic renal failure.

Previous studies have indicated that the application of low dose radiation to an arterial ligation has the potential to subsequently reduce or eliminate restenosis caused by smooth muscle cell proliferation. Sufficient kidney irradiation causes a radiation nephropathy and often leads to renal failure. In order to evaluate the effect of low-dose irradiation on the kidney we hypothesized that this particular therapy modifies renal injury in rats with renal ablation and subsequently slows the rate of the progression. For further clarification of the effect of irradiation at low doses, we determined proliferating cell nuclear antigen (PCNA) and monocyte chemoattractant protein-1 (MCP-1) expression in remnant kidneys after low-dose radiation. Adult Wistar rats (n = 10) were studied during the two weeks after renal ablation. The left kidney was irradiated 24 hours after an operation in anaesthetised animals with 3 Grey in a single dose. Ablated rats without irradiation (n = 9) served as nephrectomized animals group. Rats without surgery and without radiation (n = 10) served as healthy controls. Renal damage was assessed using the following parameters: urine protein excretion rate (UprotV, mg/day), awake systolic blood pressure (SBP, mm Hg), serum creatinine (SCr, micromol/l). The indirect immunofluorescence method was used for the detection of PCNA and MCP-1 expression. Glomerular and tubular immunostaining was scored semiquantitatively. Numerous PCNA positive cells and MCP-1 expression were present in the glomerulus and tubulointerstitium in nephrectomized rat kidneys. Low-dose radiation application was associated with a significant reduction in PCNA and low MCP-1 expression. This study shows that the application of low-dose irradiation has the potential to modify the progression of chronic renal failure in rats.

Oxidative stress status in kidney tissue after losartan and atenolol treatment in experimental renal failure.

BACKGROUND/AIMS: Rats with subtotal nephrectomy (5/6NPX) rapidly develop systemic hypertension and proteinuria. The aim of our study was to evaluate the changes in oxidative stress parameters after 2 and 4 weeks of treatment with renin-angiotensin system (RAS)-blocking agent losartan and beta-blocking agent atenolol in experimental chronic renal failure (CRF). METHODS: After 5/6NPX, rats were immediately treated with losartan or atenolol. The lipid peroxidation (LPO) products malondialdehyde and 4-hydroxyalkenals and oxidized and reduced glutathione values were measured in the renal cortex tissue and in blood; isoprostanes in urine. RESULTS: There were no differences in the blood pressure values, serum creatinine levels or in daily proteinuria using both antihypertensive treatments. Losartan treatment lowered significantly LPO in kidney tissue after 2 and 4 weeks of treatment compared with untreated and atenolol-treated animals and induced the decrease of excretion of isoprostanes in urine at the end of the study. There was no ameliorating impact of losartan or atenolol observed in the blood status of oxidative stress in this period of time. CONCLUSION: In the early period of experimental CRF, losartan treatment but not atenolol treatment induces significant decline in LPO grade in the kidney tissue of nephrectomized rats. RAS blockade in the kidney influences local tissue LPO in a much greater extent than in blood.

Decrease in laminin content and protein excretion rate after five sixths nephrectomy and low-dose irradiation in the rat.

The effect of low-dose irradiation on laminin distribution and urine protein excretion in the remnant rat kidney has been studied. The rat remnant kidney formed after 5/6 nephrectomy is an experimental model of chronic renal failure. In the remnant kidney, focal segmental glomerulosclerosis is developed characterized by focal or segmental sclerosis in glomeruli, alterations in the tubules and thickening of the glomerular basement membrane. Low dose irradiation has been presumed to suppress sclerotic processes. In this study 24 male Wistar rats were subdivided into the nephrectomized group, nephrectomized and irradiated groups (1 or 3 Grey), and healthy control group. Animals were sacrificed at 2, 4 and 8 weeks after beginning the experiment. Laminin immunohistochemical staining was found along the tubular and glomerular basement membranes in all experimental groups, but with varying intensity. Laminin content in the basement membranes was decreased in early stages (week 2), especially after irradiation followed by increase during the later stages with relatively high levels at the end of the experiment (week 8). Irradiation at a dose of 3 Grey decreased protein excretion compared to the nephrectomized rats at all stages, while 1 Grey dose was ineffective. Based on decreased proteinuria we conclude that moderate low-dose irradiation has beneficial effects on the rat remnant kidney and that laminin in basement membranes is probably not the most crucial component in regulating membrane permeability.

Impact of the supplementation of kidney mass on blood pressure and progression of kidney disease.

BACKGROUND: To test the hypothesis that nephron mass is an independent determinant of arterial pressure, the effects of augmenting renal mass by isograft transplantation were studied in the model of secondary hypertension. METHODS: The effects of isograft transplantation or sham operation on blood pressure, proteinuria, remnant kidney mass, glomerular filtration rate and glomerulosclerosis were assessed in 5/6 nephrectomized (5/6 NPX) rats. RESULTS: Systolic blood pressure was lowered on average by approximately 35 mmHg and glomerular hyperfiltration was attenuated in the remnant kidneys of transplant recipients. Markedly lower urinary protein excretion rates and glomerulosclerosis scores in the remnant kidney accompanied these supplemental transplants to values roughly one-third of those from sham-operated rats. CONCLUSIONS: The data show that reduced renal mass per se is the major factor in the development and maintenance of arterial hypertension and glomerular injury in 5/6 NPX rats and these changes can be reversed by supplementing renal mass. The data provide strong support for the notion that renal mass is a significant, independent determinant of arterial pressure.

Ultrastructural changes in the remnant kidney (after 5/6 nephrectomy) glomerulus after losartan and atenolol treatment.

The aim of our study was to investigate the effect of losartan on the changes in the early stages (at week 4) of experimental chronic renal failure after 5/6 nephrectomy compared with the impact of atenolol. Attention was focused on the ultrastructural changes in the renal corpuscles. Twenty-seven male Wistar rats were divided into three groups: nephrectomized group, nephrectomized losartan-treated group and nephrectomized atenolol-treated group. Rats were kept in a climate-controlled facility, where animals were housed under standard conditions on a 12-hour light/dark cycle and fed with standard rodent chow. Angiotensin receptor antagonist losartan (180 mg/L) or beta-blocking agent atenolol (750 mg/L) was added to the drinking water and treatment was started on the first day after the operation. Systolic blood pressure and 24 hour protein excretion was measured every week. Nephrectomized rats had higher proteinuria and systolic blood pressure than the treated rats. Rats were killed 4 weeks after surgery. Early stage renal disease was characterized by glomerular hypertrophy and focal segmental glomerulosclerosis. The morphological study revealed that ultrastructural changes in the atenolol-treated group were smaller than those in the nephrectomized and losartan-treated groups. Glomerular basement membrane (GBM) thickness was significantly increased in losartan-treated (206.8 nm) and atenolol-treated (198.8 nm) rats compared to nephrectomized (169.2 nm) rats. The podocytes demonstrated hypertrophy and foot process effacement, especially in nephrectomized group. In conclusion, our results show that firstly, treatment with losartan and atenolol significantly increased GBM thickening and secondly, treatment with atenolol reduced ultrastructural changes in the podocytes.

Beneficial effects of water-based exercise in patients with chronic kidney disease.

The possible beneficial effect of regular aquatic exercise on cardiorespiratory, renal lipid parameters and oxidative stress status was studied in patients with mild to moderate renal failure. The exercise group did low-intensity aerobic exercise in the pool during a period of 12 weeks, twice a week, with sessions lasting for 30 min. Matched control participants remained sedentary. The results showed that in the exercise group all cardiorespiratory functional parameters improved and resting blood pressure lowered significantly. Proteinuria and cystatin-C were diminished significantly and glomerular filtration rate was enhanced. To evaluate the changes in oxidative stress status in the serum, products of lipid peroxidation (LPO) and serum glutathione values were measured. LPO was reduced significantly and reduced glutathione levels showed significant improvement after the exercise-conditioning programme. In the control group the data either remained the same or worsened in the same period of time. In conclusion, regular water-based exercise has beneficial effects on the cardiorespiratory, renal functional parameters and oxidative stress status in patients with moderate renal failure, and can be used in the complex rehabilitation of chronic renal failure patients, together with blood pressure control, dietary consultation, encouragement and education to prevent physical worsening and to postpone cardiovascular and renal atherosclerotic complications.