Vitamin D and subclinical cardiac damage in a cohort of kidney transplanted patients: a retrospective observational study.

In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.

Apoptosis in the kidneys of patients with type II diabetic nephropathy.

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.

Very early alloantigen-independent trafficking of lymphocytes during ischemic acute kidney injury.

Lymphocytes play an important role during ischemia-reperfusion injury (IRI). Lai et al. have demonstrated, for the first time, an increase in kidney lymphocytes 1 hour after IRI, a newly identified kidney lymphocyte reservoir, and have confirmed the pathogenic role of lymphocytes by manipulating the sphingosine-1-phosphate (SIP)-sphingosine-1-phosphate type 1 (S1P1) receptor pathway.

Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state.

To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P<0.004) in HD patients. Both IL-6 protein and IL-6 mRNA expression were increased in muscle of inflamed CKD patients vs controls (P<0.05). Although muscle net protein balance was similar in all patients, it was significantly more negative in HD patients with high than in those with low IL-6 plasma levels (P<0.05). In addition, net protein balance was related to the forearm release of IL-6 in HD patients only (r=0.47; P<0.038). These data demonstrate that IL-6 expression is upregulated in muscle, and that muscle tissue, by releasing this cytokine, may contribute to the inflammatory response in HD patients. The release of IL-6 from peripheral tissues is associated with an increase in muscle protein loss in HD patients, suggesting that muscle release of IL-6 is linked to protein catabolism in these patients. The release of IL-6 from peripheral tissues may act as a signal for the inflammatory response and contribute to functional dysregulation in uremia.

Gender and the progression of chronic renal diseases: does apoptosis make the difference?

Several studies in patients with chronic kidney diseases have shown that men have a more rapid disease progression than women. Also, with ageing, men exhibit greater decrements in renal function and increased glomerular sclerosis than women. Data from meta-analysis studies indicate that women with several non-diabetic renal diseases such as membranous nephropathy, IgA nephropathy and polycystic kidney disease present a slower progression, but in diabetic renal disease this is not yet established. Thus, men appear to be at greater risk for renal injury than are women, but the underlying mechanisms are unknown. Sex hormones may mediate the effects of gender on chronic renal disease, through the interaction with the renin-angiotensin system, the modulation of nitric oxide synthesis and the downregulation of collagen degradation. New observations indicate that androgens may contribute to continuous loss of kidney cells though the stimulation of apoptotic pathways. Apoptosis is an unique type of programmed cell death which is activated in several chronic kidney diseases. Studies in vitro indicate that androgens prime a Fas/FasL dependent apoptotic pathway in kidney tubule cells. This apoptotic cell death pathway is receptor-linked and interacts with the mitochondrial pathway, which may be activated by other mechanisms, such as toxins and ischemia. Therefore, the mechanisms to cell death which are primed by androgens may interact with others occurring in several conditions leading to the loss of renal cells. These findings are consistent with a role for androgens to promote chronic renal injury in men.

Apoptosis induced by serum withdrawal in human mesangial cells. Role of IGFBP-3.

Apoptosis has been reported to occur both during the course of kidney development and the progression of kidney injury to scarring. Insulin-like growth factor binding protein-3 (IGFBP-3), a component of the IGF system, has been shown to induce apoptosis in cancer cell lines. However, if IGFBP-3 has similar effects in human mesangial cells (HMC) remains unknown. The purpose of this study was to examine the expression of IGFBP-3 and its possible effect on the induction of apoptosis in HMC during serum deprivation. We have observed that IGFBP-3 accumulates progressively in HMC in which serum has been withdrawn. In these cells, an increase of IGFBP-3 is observed before the production of apoptosis suggesting a link between these phenomena. Furthermore, the addition of IGFBP-3 in physiological amounts (from 100 to 400 ng/ml) to culture medium devoid of growth factors accelerates and increases the apoptotic process with a dose-dependent effect. These findings suggest that IGFBP-3 is a mediator of cell death in human mesangial cells when the availability of growth factors is curtailed. These data also suggest that IGFBP-3 could contribute to apoptotic processes observed in human disease.

[Insulin-dependent diabetes and pregnancy. A model of coordinated approach]. / Diabete insulino-dipendente e gravidanza. Un modello di approccio coordinato.

A historical account of the relation between diabetes and pregnancy is followed by the presentation of a personal series of 10 insulin-dependent diabetic pregnant women (3 White's class B, 2 class C, 3 class D and 2 class F/R) treated in accordance with a newly applied quarterly and fortnightly protocol. Nearly normal blood sugar (HbA1 maintained around 8% in the second and third trimester) was achieved through home blood glucose self-monitoring, in keeping with the Karen Bruni Centre's educational programme. This includes self-management of intensified insulin treatment in the form of 2-3 injections per day (Monotard MC and HM, Actrapid MC and HM), as well as the use of Novo Pen (100 U/ml Actrapid HM) for supplementary insulinisation. Average insulin initial dose: 0.51 U/Kg/day (range 0.2-0.7); final dose 0.83 U/Kg/day (range 0.6-1.2). Delivery was by caesarean section on obstetric indication: 9 at the 36th week, 1 at the 34th for trisymptomatic gestosis. There were no foetal nor neonatal death. All children were subjected to intensive neonatological care. There were 3 cases of macrosomia and 1 tetralogy of Fallot, which followed a benign course. Despite their absence of statistical value, these data show that optimised multidisciplinary treatment can be of utility in preventing neonatal morbidity and mortality in an insulin-dependent diabetic pregnancy. They also indicate that a coordinated treatment model can equally be put into effect even in a non centralised structure, provided certain facilities exist: in our case, voluntary support on the part of Karen Bruni Diabetic Association, obstetric interest in diabetology and a neonatological background for treatment of the offspring of diabetic mothers. Lastly, this series substantiate the effectiveness of the programme of self-checking and self-management of diabetes in the accomplishment of "optimised" blood glucose control and containment of costly hospitalisation at the time of delivery.

[Importance and usefulness of transcutaneous PO2 in neonatology. Experience with the healthy and sick neonate]. / Importanza ed utilita' della PO2 transcutanea in neonatologia. Esperienze nel neonato sano e in quello malato.

The authors have checked transcutaneous PO2 in newborns in the Neonatology Department of Maria Vittoria Hospital, Torino, Italy. 39 full-term newborns (healthy, Apgar score more than 7) have been monitorized during their first minutes. The results have been divided in four groups: spontaneous birth or caesarean section with fetal suffering or not. Significant differences have been shown between newborns with fetal suffering whether they were born by caesarean section or not, and between born by caesarean section with or without fetal suffering. 27 newborns with gestational age of 32 weeks or less have been monitorized all the time they were in need of oxygen therapy. 29,6% of these babies have shown, during the first week of life, at least one peak of tcPO2 more than 100 torr. The authors insist on the importance of tcPO2 monitoring during the first moments of life, on the influence of labour conditions and type of birth. In preterm neonates treated with oxygen therapy, tcPO2 is now the best method to evaluate hypoxia (leading to cerebral lesions) and hyperoxia (with risk of retinal and pulmonary damage).

[Perinatal mortality in various weight classes: evaluation of data of the Ospedale Maria Vittoria, Turin 1977-1981]. / Indagine sulla mortalita' perinatale per classi di peso: valutazione dei dati dell'Ospedale Maria Vittoria di Torino negli anni 1977-1981.

The authors have studied stillbirth, early neonatal death rate, perinatal death rate following weight classes, weight distribution in live born and death causes between 1977 and 1981. These data permit to evaluate the degree of efficiency in the obstetrical and neonatological department. Weight distribution pattern has been fairly constant and low-weight incidence similar to that found by other authors. Perinatal death rate has remained stable in time around 11,4%. Still births have increased particularly in weight classes between 1001 and 2000 g. Early newborn death rate has decreased in weight classes between 2001 and 2500 and over 4000 g. Asphyxia was the most frequent death cause in weight classes between 1501 and 2000 g and between 2501 and 4000 g. These data are similar to those found in british and swedish studies. The authors insist that every effort must be made to reduce not only perinatal death rate but also to prevent future handicaps.