ABSTRACT
It is known to few that the path to the discovery of the long-denied plasma creatinine and its clearance was long and difficult. For quite a long time, related controversies between ...different groups of researchers were widespread and heated. The scientists who have dealt with the related problems are among the most famous of the last century and some of them are part of the history of medicine. Giovanni Ferro-Luzzi, an Italian clinician, was one of these researchers. He was among the first to detect and dose plasma creatinine and the first ever to measure the clearance of endogenous creatinine (CrCl). Unfortunately, due to a series of unforeseeable events, he has been completely forgotten together with his undertakings. In this review we retrace the steps that led to the measurement of plasma creatinine, and CrCl. With brief biographical notes we try to explain the oblivion of this important figure and of his nephrological accomplishments.
Pulmonary arterial hypertension (PAH) and renal thrombotic microangiopathy (rTMA) are rare diseases in childhood, frequently leading to death and end-stage renal disease, respectively. Their combined ...occurrence has been reported anecdotally. We investigated the clinical, biochemical, and genetic aspects of 5 children with the rare combination of PAH and rTMA. Onset of disease ranged from 1.5 to 14 years of age. The 2 youngest patients presented with concomitant pulmonary and renal disease; in the older patients, PAH was preceded by rTMA from age 2.5 to 7 years. Three patients presenting at ≤ 3 years of age died of right ventricular failure secondary to progressive PAH. In 2 patients, cobalamin C (cblC) deficiency was diagnosed postmortem. Three patients were treated with hydroxocobalamin; 1 died 2 weeks after diagnosis, 1 patient exhibited progressive pulmonary vasculopathy, and 1 patient is currently in stable condition. cblC deficiency was diagnosed biochemically 2 days to 18 years after initial presentation. Genetic analysis confirmed mutations in MMACHC in all patients; 4 patients were compound heterozygous, with all having base-pair substitutions (G>A or G>T) at nucleotide 276 in addition to frame-shift mutations. One patient had homozygous nonsense mutations of MMACHC. We established cblC deficiency as the denominator in the rare combination of PAH and rTMA in these children. Early recognition of cblC deficiency and vigorous treatment with hydroxocobalamin may beneficially affect the course of this devastating disease.
Background. Patients with atherosclerotic renovascular disease (ARVD) are almost invariably treated by revascularization. However, the long-term outcomes of this approach on survival and progression ...to renal failure have not been investigated and have not been compared with that of a purely medical treatment. The aim of this observational study was to investigate factors affecting long-term (over 5 years) outcome, survival and renal function of patients with ARVD treated invasively or medically. Methods. ARVD was demonstrated angiographically in 195 patients who were consecutively enrolled into a follow-up study. Patient age was 65.6±11.2 years, serum creatinine was 1.74±1.22 mg/dl and renal artery lumen narrowing was 73.5±17.5%. A revascularization was performed in 136 patients, whereas 54 subjects having comparable characteristics were maintained on a medical treatment throughout the study; five patients were lost during follow-up. Results. The main follow-up was 54.4±40.4 months. The assessment of cardiovascular survival and renal survival at the end of follow-up revealed 46 cardiovascular deaths, 20 patients with end-stage renal disease (ESRD) and 41 patients with an increase in serum creatinine of over one-third. The multivariate analysis showed that renal revascularization did not affect mortality or renal survival compared with medical treatment. Revascularization produced slightly lower increases in serum creatinine and a better control of blood pressure. A longer survival was associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) (P = 0.002) in both revascularized and medically treated patients. The only significant predictor of ESRD was an abnormal baseline serum creatinine. Conclusions. On long-term follow-up, ARVD was associated with a poor prognosis due to a high cardiovascular mortality and a high rate of ESRD. In our non-randomized study, revascularization was not a major advantage over medical treatment in terms of mortality or renal survival. The use of ACEIs was associated with improved survival.
We aimed at comparing the relationship of reduced estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) and mortality between high risk patients with and without type 2 ...diabetes mellitus (T2DM). The cross-sectional study evaluated 16,298 participants (1,627 T2DM) acutely admitted to hospital. The longitudinal study comprised 7,508 patients (673 with diabetes and 6,835 without). eGFR was categorized into 6 stages from >90 to <15 mL/min/1.73 m2. Kidney dysfunction was defined by an eGFR < 60 mL/min/1.73 m2. Patients with T2D showed a higher prevalence of CVD (37.9% versus 23.6%; P<0.001) and kidney dysfunction (25% versus 13.2%; P<0.001) than in the general population. An association with CVD was found with eGFR stages from 30 to 90 mL/min/1.73 m2 in T2D and from <15 to 90 mL/min/1.73 m2 in general population, in whom the association of eGFR with coronary heart disease was in an inverse relationship (P<0.01 for trend). Survival, in diabetes, was lower (P=0.037) but not associated with kidney dysfunction. Conclusions. In a high risk population, patients admitted to hospital, the relationship of kidney function with CVD is different between T2D and the general population. Competing mortality and the presence of other major risk factors in diabetes may be responsible for this difference.
Background
The cardiovascular risk associated with an increase in serum creatinine below the acute kidney injury (AKI) threshold, during hospitalization, has not been studied in depth. We assessed ...patients’ features and outcomes associated with these changes.
Methods
Retrospective cohort study of 12,493 consecutive patients admitted to hospital throughout 12 months. We investigated the patients who had a small creatinine increase (SISCr) between 1.2 and <1.5 times the admission value, and tested the association of creatinine changes with the prevalence of cardiovascular disease (CVD). In a follow-up study, we assessed the all-cause mortality and its relationship with SISCr.
Results
Among patients with two or more creatinine measurements, 14.9% showed a SISCr. Older age, female gender and higher estimated glomerular filtration rate (eGFR) at admission were characteristics of these patients. The prevalence of CVD was 14.6% in patients with SISCr vs. 10.7% in those with stable creatinine (p < 0.001). SISCr was detected in 36, 26.6 and 18.9% of chronic heart failure (CHF), chronic ischemic heart disease (CIHD) and acute myocardial infarction (AMI) patients, respectively. The follow-up was 26.7 ± 10.6 months with 770 all-cause deaths. Serum creatinine increase above 20% was associated with a significant higher mortality compared to changes below 20%, adjusted hazard (HR) ratio 1.577 (p < 0.001). A higher risk was found associated with creatinine increases >1.5 times the baseline: HR 1.704 (p < 0.001).
Conclusions
In hospitalized patients, increases in serum creatinine below the AKI threshold are associated with CHF, CIHD and long-term mortality.
BACKGROUND AND OBJECTIVES
A postdialytic increase in blood pressure (BP) is a recognized but often an overlooked complication. The epidemiology and predisposing factors are still not well defined. We ...studied a large sample of Italian dialysis patients to assess the prevalence of postdialysis hypertension (PDHYPER), defined as any increase of systolic BP (SBP) >10mm, Hg above the predialysis value, the associated factors and its role in cardiovascular (CV) mortality.
PATIENTS AND METHODS
In this observational study, we assessed dialysis associated changes in BP in 4,292 hemodialysis (HD) patients over 1 month (51,504 sessions). We compared the clinical characteristics of the patients with stable BP values during the HD session with those with PDHYPER. We also assessed the impact of PDHYPER on CV mortality.
RESULTS
A total of 994 (23.1%) patients had PDHYPER. Patients with PDHYPER were more likely to be hypertesive, older, have a shorter dialysis vintage, be male, have lower SBP, lower changes in weight during HD, and receive more antihypertensive medications. These predictive factors were shown to be associated with an interaction between weight loss and dialysis, suggesting a volume-related mechanism in its pathogenesis. PDHYPER was also associated with CV mortality.
CONCLUSIONS
In our study on a large Italian cohort of dialysis patients, the prevalence of PDHYPER was higher than what was previously reported and is a significant risk factor for CV mortality in dialysis patients. The pathogenesis is multifactorial but hypertensive state, antihypertensive medications, and extracellular volume expansion appear to play a major role.
Background
New creatinine based equations for estimating glomerular proposed for aged subjects have not been assessed in their association of reduced eGFR with cardiovascular (CV) morbidity or all ...cause (AC) mortality.
Patients
All subjects ≥70 years old (2998) who had been admitted to the hospital during a 12 month period were examined.
Methods
In a cohort study we applied the new Berlin Initiative Study (BIS1) equation. We compared the association of reduced eGFR estimated by BIS1 and MDRD equations, with cardiovascular (CV) disease and all cause (AC) mortality.
Results
eGFR was 57 ± 17 mL/min/1.73 m
2
by MDRD and 71 ± 28 mL/min/1.73 m
2
by BIS1 (P < 0.001). A diagnosis of CV disease was present in 947 patients. CV disease was associated with eGFR < 60 mL/min/1.73 m
2
by both formulas: OR 1.179 (CI 1.001–1.390) for BIS1 and OR 1.440 (CI 1.223–1.696) for MDRD. In survival analysis a significant association of eGFR < 60 mL/min/1.73 m
2
with AC mortality was found for both equations: MDRD (HR = 1.270, CI 1.111–1.453, P < 0.001), BIS1 (HR = 1.174, CI 1.031–1.338, P = 0.016). The analysis repeated with groups of age showed that the association of mortality with eGFR
BIS1
< 60 mL/min/1.73 m
2
was lost over 80 years.
Conclusions
In patients >70, admitted to hospital, the implementation of the new BIS1 estimating equation does not modify the relationship, observed with the MDRD formula, of reduced GFR with CV disease or AC mortality.
A historical research was made on papers published by Italian scientists on cardiorenal diseases. The investigated period is between the beginning of the 20th century and the entry of Italy into the ...Second World War, 1940. 34 papers dealing with the relationship between the kidney and the cardiovascular system were retrieved. All but two articles were published in Italian medical periodicals. The topics covered are varied and range from cardiotoxicity of substances in uremia to the role of renal disease in vascular damage. Some articles are forerunners of later pathophysiological concepts and research technologies. These concern early atherosclerotic vascular damage and the presence of dialyzable cardiotoxic substances in renal insufficiency. Unfortunately, these highly innovative researches have had little diffusion and have fallen into oblivion in Italy and abroad. In conclusion, our research shows that in the first half of the 20th century in Italy there was a lively interest in cardio-renal diseases and that some researchers had produced precursor results of what was confirmed many years later.
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