[Acute renal failure--the present and perspectives]. / Insuficienta renala acuta--prezent si perspective.

Acute kidney injury is a common complication in hospitalized patients, and its incidence has risen significantly in the past 15 yr. Despite significant technical advances in therapeutics, the mortality and morbidity rates associated with acute kidney injury remain dismally high and have not appreciably improved during the past four decades. An ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury, acute tubular necrosis, early and accurately and may aid to risk stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay, and mortality. The major types of urinary biomarkers fall into three classes: 1) inflammatory; 2) renal tubular proteins that are excreted into the urine after injury; 3) surrogate markers of tubular injury. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that permit earlier and more accurate diagnosis.

Hemoglobin normalization trials in chronic kidney disease: what should we learn about quality of life as an end point?

This editorial review takes an in-depth look to the effect of hemoglobin (Hb) normalization with erythropoietin on quality of life (QoL) in chronic kidney disease (CKD). The analysis of the current available data shows major inhomogeneities in the tools used for assessment of QoL and in data reporting. Furthermore, the major trials on Hb normalization were generally not primarily designed to analyze QoL as a specific end-point. However, current data suggest that only partial correction of anemia with EPO may improve QoL, whereas correction of Hb to above 12 g/dL does not exert any positive effect. Finally, the authors provide recommendations on a more rigorous assessment of QoL in future trials in CKD patients.

[The management in chronic kidney disease (CKD)]. / Noi strategii terapeutice in boala cronica de rinichi.

Renal fibrosis is the principal process underlying the progression of chronic kidney disease (CKD) to end stage renal disease (ESRD). It is a relatively uniform response involving glomerulosclerosis, tubulointerstitial fibrosis and changes in renal vasculature. Direct or indirect tubulointerstitial injury via oxidative stress and various effector molecules trigger cellular responses like tubular epithelial cell (TEC) apoptosis, activation of fibroblasts and their phenotypic switch to myofibroblasts, proliferation of macrophages, fibrocytes, fibroblasts as well as epithelial to mesenchimal transition of TEC. In this review we explore the potential of experimental therapeutic strategies, based on preventing or reversing the pathophysiologic steps of kidney remodeling that lead to fibrosis.

[Stage 3-5 chronic kidney disease--what is the real prevalence in Romania?]. / Boala cronica de rinichi in Romania: care este prevalenta reala in populatia generala adulta?

UNLABELLED: A high prevalence of reduced GFR has been reported in Western populations. However, little is known about the real prevalence of chronic kidney disease (CKD) in Eastern Europe. Our aims were 1) to identify the true burden of CKD in a large adult population sample; 2) to compare the GFR estimates by the "classic" MDRD4 formula with the GFR derived from the formula proposed recently by Levey. METHODS: Data from 19.509 consecutive Caucasian adult ambulatory patients, referred to two laboratories affiliated to two regional referral centers in Romania, were recorded. Collected data were on age, gender, and serum creatinine (Scr). For one center, total cholesterol, LDL- and HDL-cholesterol, and Hb values were also available. GFR was determined by the classic four-variable MDRD formula (MDRD4) GFR1 = 186 x Scr(-1.154) X age(-0.203) (x 0.742 if female) and by the new MDRD formula (modMDRD4): GFR2 = 175 x corrected Scr(-1.154 x age(-0.203) (x 0.742 if female). RESULTS: 19394 patients (mean age 47.7 years, 39.1% males, mean Scr 0.9 mg/dL) were analyzed. The prevalence of CKD (defined as GFR < 60 ml/min/1.73 m2) was 8.8% (according to MDRD4), and 11.7% (modMDRD4). Therefore, 506 patients (5%) classified by the "classical" MDRD4 formula with a GFR1 of 60-89 mL/min/1.73 m2 have in fact CKD. Stage III CKD was present in 10.74% of patients (males 9.04%, females 11.82%), stage IV CKD in 0.57% (0.72%-0.47%), and stage V in 0.39% (0.29-0.45%). As expected, in the elderly population, the burden of CKD is much higher: 39.74%, with 9.30% of elderly having GFR severely reduced (< 45 ml/min). The prevalence of end-stage renal disease was at least double in the elderly compared to non-elderly. There was a linear relationship between anemia occurrence, lipid abnormalities, and GFR reduction. CONCLUSION: The prevalence of chronic kidney disease in this large Eastern European unselected population is high (8.8-11.7%), similar to the NHANES III population. Almost 40% of elderly subjects have reduced GFR, with one in 10 patients having a severe reduction of renal function.

Diabetes, kidney disease and anaemia: time to tackle a troublesome triad?

Both chronic kidney disease (CKD) and type II diabetes mellitus (DM) are increasing in frequency among Western populations and both are potent risk factors for the development of anaemia. The presence of CKD and diabetes together represent the most important aetiopathogenic combination for the development of anaemia. New evidence has highlighted some of the underlying mechanisms which make diabetic patients more susceptible to dyserythropoiesis, particularly once they have developed concomitant CKD. In addition, recent publications from large-scale epidemiological studies have highlighted the impact of anaemia on diabetic patients. The purpose of this review was to focus on the pathophysiology and impact of anaemia in DM.

[Epidemiology of biopsy-proven renal disease in Romania: data from a regional registry in north-eastern Romania]. / Epidemiologia bolii renale în Romania trecere în revista a bazei de date regionale de biopsii renale din zona Moldovei (1995-2004).

Unlike Western European countries, data on the epidemiological biopsy-proven renal disease in Eastern Europe is scarce. We aimed to analyze retrospectively the main histological renal findings, over a 10-year (1995-2004) period, in a large tertiary nephrology referral center in North-Eastern (N-E) Romania, serving a population of 4.7 million inhabitants. Clinical and biological data were also collected and correlated with histological findings. 336 renal biopsies were finally analyzed. The distribution of major clinical syndromes was: nephrotic syndrome (52%), followed by acute renal failure (19%), mild-to-moderate chronic renal failure (17%), nephritic syndrome (8%) and asymptomatic urinary abnormalities. 56.6% and 32.2% were primary and secondary glomerulopathies (GN), respectively, whereas vascular nephropathies and tubulointerstitial nephritis accounted for only 3.6 and 2% of the diagnoses. Overall, membranoproliferative (MPGN) (38%) and mesangioproliferative (MesGN) GN's (19%) were the most common primary glomerulopathies. A progressive significant decrease in the incidence of MPGN and an increase in MesGN over time were seen in our center. Analyzing other Romanian regional data, also a geographical "shift" in the prevalence of the most common primitive GN's from Eastern (E) to Western (W) Romania, similar to the N to S gradients across Europe was noted: there is a high prevalence of MPGN in the E, and a high prevalence of MesGN (including IgA nephropathy) in W Romania. These important differences in the prevalence of the most common primary GN's in E Romania may be due to lower income, education, and infrastructure levels. This hypothesis is strengthening by the higher prevalence of post-infectious and, possible, vasculitis-related GN in E Romania.

[The first case of coronary artery by-pass grafting surgery (CABG) in a patient on maintenance dialysis in Iasi]. / Prima operatie de by-pass coronarian la un pacient dializat cronic în Iasi.

Coronary artery disease has a significantly higher prevalence in chronic dialysis patients compared to the general population, explained by a cluster of non-specific and specific (uremia-associated) cardiovascular risk factors, typical for these patients. Nephrologists and cardiovascular surgeons worldwide are rather reluctant to offer CABG to dialysis patients, because of concerns about higher risks associated with this procedure in this frail population. However, there is an increasing opinion supporting a more aggressive management of coronary artery disease in uremic individuals. To illustrate this "positive attitude", we report here the first dialysis patient ever treated by CABG in Iasi; his good outcome was both rewarding and encouraging for us all.

Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients.

BACKGROUND: Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). METHODS AND RESULTS: 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding the percentage luminal reduction of the most severe lesion in each artery. Patients with normal angiograms had significantly less arterial stiffness (as reflected by both a lower PWV=8.42+/-1.53 m/s and a lower AIx=17.9+/-5.55 %) compared with the 35 subjects with evidence of obstructive coronary disease at angiography (PWV=9.21+/-1.15 m/s and AIx=23.4+/-5.4 %, P<0.05 for both). Moreover, as more coronary vessels were affected, PWV and AIx increased proportionally. Based on receiver operating characteristics (ROC) curve analysis mean PWV levels showed an optimal cut-off point at 8.35 m/s (sensitivity=0.77; specificity=0.60), while mean AIx levels showed an optimal cut-off point at 17% (sensitivity=0.87; specificity=0.70). There was a statistically significant linear relationship between the atherosclerosis burden and both measures of arterial stiffness: PWV (r=0.31, p=0.007) and AIx (r=0.46, p=0.003). Independent predictors for the arterial stiffness parameters in this CKD population (multiple stepwise regression analysis) were age (r=0.69 for PWV and r=0.62 for AIx), and mean arterial pressure (MAP) (for AIx, p<0.0001). CONCLUSION: This study provides the first direct evidence in a cross-sectional investigation that PWV and AIx are related to the extent of coronary obstruction in CKD patients.

[Major impact of arteriosclerosis on cardiovascular morbidity and mortality]. / Impactul major al rigiditatii arteriale (arteriosclerozei) asupra morbiditatii si mortalitatii cardiovasculare.

Arterial stiffness (arteriosclerosis) is a diffuse process affecting the media of large arteries, strongly linked to the process of ageing, but influenced by several other major factors like hypertension and vascular calcifications. Arteriosclerosis has been recognized in recent years as a novel non-traditional cardiovascular risk factor both for renal and non-renal general population. Two of arterial stiffness parameters, pulse wave velocity and the augmentation index--determined by applanation tonometry, are strongly correlated with cardiovascular morbidity and mortality, as well as with the general mortality. Arterial stiffness, due to several factors related to the uremic milieu, is more pronounced in patients with end-stage renal disease compared with patients without renal dysfunction. The authors are briefly reviewing the most recent literature regarding the impact of arterial stiffness on cardiovascular outcome. Identifying the factors associated with reduced arterial compliance may positively influence cardiovascular outcome in the general population, and particularly in renal patients, plagued by a high burden of cardiovascular disease.

[Retrospective study of 97 ANCA-positive patients: epidemiologic and clinical spectrum]. / Analiza retrospectiva a 97 de cazuri cu ANCA pozitivi: aspecte epidemiologice si clinice.

UNLABELLED: We analysed the clinical profile of antineutrophil cytoplasmic antibodies (ANCA) positive patients in a retrospective study including all cases of ANCA positivity (determined by ELISA) from the Nephrology Clinic, Parhon University Hospital Iasi during the interval 1998-2003. There were 97 ANCA positive patients (mean age 43.7 s18-75t years, female/male ratio 1.55), of whom almost two thirds had c-ANCA, almost one third p-ANCA, while 9 patients had both types of antibodies. The incidence was 22.5/pmp for the North-Eastern province of Romania. Just 19.3% from the suspected cases with ANCA-associated disease were positive for these antibodies. 47.7% had systemic vasculitis (10 with microscopic polyangiitis--MA, 6 with Wegener's granulomatosis--WG, 1 with Churg-Strauss angiitis, 29 with non-specific vasculitis--NSV). Twenty-seven (27.8%) had connective tissue disease--CTD (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, systemic sclerosis, mixed connective tissue disease, and sarcoidosis), while in 5 cases ANCA were associated with other diseases. Nine cases presented with rapid progressive glomerulonephritis (RPGN) without signs of systemic involvement, and other ten with advanced chronic renal failure (CRF). The most frequent clinical manifestations involved the kidney (71%), the skin, the muscles and joints, and the cardiovascular system. CONCLUSIONS: ANCA positivity is associated with a wide spectrum of diseases, mostly with CTD and NSV. c-ANCA was predominantly seen in WG and advanced CRF, while p-ANCA was associated with MA. In nonspecific vasculitis and connective tissue diseases, both patterns were present. We recommend ANCA determination as a screening method in all cases with renal dysfunction and nephritic syndrome and/or with signs of systemic vasculitis and/or collagenosis.

Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients.

BACKGROUND: Patients with end-stage renal disease on dialysis have among the highest cardiovascular event rates documented. Abnormal nitric oxide (NO)-dependent endothelial reactivity and increased arterial stiffness are commonly described in hemodialysis (HD) patients. Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AGI)--have been shown to be powerful predictors of survival on hemodialysis. It is not known how these parameters interfere with successful renal transplantation. METHODS: PWV and aortic AGI (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD patients (20 men; age, 41.8 years) and in a control group of 20 patients with essential hypertension (HTA) (10 men; age, 43.6 years). Twenty of the HD patients (10 men; age, 39.7 years) received live-related renal transplants (RTx) and were restudied (3 months after RTx, normal serum creatinine). NO-dependent and NO-independent vascular reactivity were assessed by changes in AGI after challenges with inhaled salbutamol (SAL) and sublingual nitroglycerin (NTG), respectively. RESULTS: AGI values were significantly lower in RTx patients compared with subjects on hemodialysis (15.9 +/- 13.9% vs. 27.9 +/- 11.9%, P<0.05), but similar to essential HTA controls (16.5 +/- 17%). Serial AGI measurements showed that successful renal transplantation is associated with a decrease in AGI in all cases, from a mean of 25.1 +/- 7.8% while on dialysis to 15.9 +/- 7.0% 3 months after transplantation (P<0.0001). The responsiveness to both endothelium-dependent stimuli (inhaled SAL) and endothelium-independent stimuli (sublingual NTG) was greater in transplant patients than in hemodialysis patients (SAL-induced decrease in AGI -82.3 +/- 65.7% vs. 45 +/- 72.3%, P<0.01; and NTG-induced decrease in AGI 197 +/- 108 vs. -129.0 +/- 215.5%, P<0.01). PWV values in dialysis patients (7.19 +/- 1.88 m/sec) were significantly higher than those measured in essential HTA patients (6.34 +/- 1.32 m/sec, P<0.05) with normal renal function (despite similar blood pressure levels). PWV after RTx was 6.59 +/- 1.62 m/sec, significantly different from pretransplantation (dialysis) values (P<0.05 for comparison) but similar to the control group of essential HTA patients. CONCLUSIONS: Renal transplantation is associated with marked improvements in vascular structure and function to a profile comparable to essential HTA patients.

What added value does ambulatory blood pressure monitoring brings to the management of post renal transplantation hypertension?

OBJECTIVE: To evaluate BP control, white coat hypertension (WCH) and abnormal circadian variability in a significant outpatient sample of renal transplant (RTx) subjects, normotensive at the last regular visit. METHODS: ABPM (Spacelab 90217) was performed every 15 min between 07:00-23:00 h and every 30 min between 23:01-06.59 h. in all patients (N = 68, 39M, S-Cr. = 153 +/- 49 mumol/l) normotensive at their last regular office BP (O-BP) measurement and with available BP records for the 12 months preceding RTx and 6 months preceding ABPM. RESULTS: BP values were frequently abnormal in this RTx cohort considered to have a satisfactory BP control. O-BP (measured with a Hawksley random-0 sphygmomanometer on the day of ABPM) was 135.5/80.6 mmHg, 47.1% of the patients with abnormal BP values. By comparison, ABPM showed a lower prevalence of uncontrolled BP: 44.1% for 24 h.-BP and only 35.3% for the daytime awake period, with values of 134.5/80.4 and 135.3/81 mmHg respectively (P = NS from O-BP). The prevalence of WCH was 12%. 24-h SBP is related to O-SBP (r = 0.71, P < 0.01) and Bland-Altman analysis demonstrates that > 95.6% of all differences between systolic ABPM and O-BP values are within +/- 2SD of the identity line. However, although 24-h DBP is equally related to O-DBP (r = 0.64, P < 0.01), on Bland-Altman analysis, 8.8% of the differences between diastolic ABPM and O-BP values are outside +/- 2SD of the identity line. Thus, systolic but not diastolic O-BP correlates with, and can be substituted to ABPM derived values. Non-dipping was frequent, regardless of the definition of normal nocturnal BP fall (10 mmHg or 10% of the daytime SBP): 82.4%, 89.7%. Even if normality was strictly defined as a night/day ratio < 0.90 for SBP and < 0.92 for DBP, non-dipping prevalence was high 73.5%, with more than one-third of the RTx patients having nocturnal hypertension (ratio > 1). CONCLUSIONS: BP control is not optimal in one-third of a typical RTx population. Furthermore, nocturnal hypertension is a frequent and underestimated phenomenon in this population. There is a good agreement between ABPM derived and casual systolic values. Office measurements, due to WCH, are under-evaluating the quality and efficacy of the antihypertensive regimens.

[Cardiovascular risk after renal transplantation(II): ischemic heart disease, hypercholesterolemia, hyperhomocysteinemia and smoking]. / Riscul cardiovascular dupa transplantul de grefa renala (II): cardiopatia ischemica, hipercolesterolemia, hiperhomocisteinemia si fumatul.

Cardiovascular disease is the main cause of death in end-stage renal failure treated by hemodialysis or peritoneal dialysis. Though reduced in renal transplant recipients compared to the dialysis population, an excess cardiovascular mortality is still present after transplantation. The authors are reviewing the main data on mortality in the renal transplant population, focusing on major risk factors: ischaemic heart disease, hypercolesterolemia, smoking, hyperhomocysteinemia. The presence of these factors and the extent of cardiac and vascular abnormalities in the dialytic patient are closely related to outcomes in the post-transplant period. It is thus mandatory to approach and minimize all these in the dialytic and even predialytic period of chronic renal failure in order to reduce renal transplant mortality in patients with functioning grafts. Finally, an algorythm in managing cardiovascular disease pre- and post-transplantation is proposed.

[Post-rifampicin acute renal failure--serious, but seldom recognized complication of the anti-tuberculosis treatment]. / Insuficienta renala acuta post-rifampicina--complicatie redutabila, însa putin cunoscuta a tratamentului tuberculostatic.

Post-rifampicin (RMP) acute renal failure (ARF) is a complication seldom recognized of the antiTB treatment worldwide. The renal failure which occurs especially after intermittent administration of RMP is most frequent due to acute interstitial nephritis by allergic mechanism. In our study we found very few cases of acute tubular necrosis or glomerular lesions revealed by rapidly progressive glomerulo-nephritis or nephrotic syndrome. The renal lesions, accompanied by anuria and usually needing hemodialysis, were associated to auto-immune hemolytic anemia, trombocytopenia, hepatic failure and gastro-intestinal disturbances. The authors review their experience (60 cases), representing about half of the cases published worldwide. The main causes of this high prevalence of post-RMP ARF in Romania are discussed: intermittent twice-a-week RMP treatment, high incidence of TB, lack of compliance to treatment, possible contribution of some by-substances in RMP capsule. We described the clinic, biology and evolution of this dangerous and underestimated entity. We compared our experience with the published data, discussing the etiology and pathogenesis, trying to design the fine portrait of this ailment.

[The cardiovascular risk after renal transplantation (1): Hypertension and left ventricular hypertrophy]. / Riscul cardiovascular dupa transplantul de grefa renala (I): Hipertensiunea arteriala si hipertrofia ventriculara stânga.

Cardiovascular disease is the main cause of death in end-stage renal failure treated by hemodialysis or peritoneal dialysis. Though reduced in renal transplant recipients compared to the dialysis population, an excess cardiovascular mortality is still present after transplantation. The authors are reviewing the main data on mortality in the renal transplant population, focusing on major risk factors: hypertension, left ventricular hypertrophy. Chronic immunosuppression is also discussed in this context, as a major determinant of blood pressure elevation after renal transplantation. The presence of these factors and the extent of cardiac and vascular abnormalities in the dialytic patient are closely related to outcomes in the post-transplant period. It is thus mandatory to approach and minimize all these in the dialytic and even predialytic period of chronic renal failure in order to reduce renal transplant mortality in patients with functioning grafts.