Living with Gitelman disease: an insight into patients’ daily experiences.
Nephrol Dial Transplant. 2012 Feb 14;
Authors: Caiata-Zufferey M, Zanini CA, Schulz PJ, Syrén ML, Bianchetti MG, Bettinelli A
Abstract
BACKGROUND: Gitelman disease presents with musculoskeletal complaints and fatigue. Surprisingly, there is no clear-cut correlation between biochemical abnormalities and symptoms.METHODS: Starting from the hypothesis that the way patients comprehend their illness within their sociocultural frameworks reflects on their way of adapting to it, this study investigated how adult patients experience the disease in everyday life. We conducted a qualitative analysis based on interviews with 12 patients. Interviews were audio recorded, fully transcribed and analyzed using the constant comparative method described by Strauss and Corbin.RESULTS: A typology of the experiences emerged from the data and was tested on each transcript with an explicit search for disconfirming cases. Patients fell into four main groups: (i) those considering Gitelman disease a disabling illness, (iI) those considering it a normalized illness, (iii) those considering it a different normality and (iv) those considering it an episodic disability. Each pattern of experience was characterized by particular (i) ways of interpreting symptoms (ii) ways of managing Gitelman disease in everyday life, (iii) general lifestyles and (iv) risks for the patient’s psychosocial life.CONCLUSIONS: These findings suggest that health care providers should take advantage of considering patients’ own perception of the disease in order to adjust the care and advice provided.
PMID: 22334612 [PubMed - as supplied by publisher]
Genetic causes of focal segmental glomerulosclerosis: implications for clinical practise.
Nephrol Dial Transplant. 2012 Feb 14;
Authors: Rood IM, Deegens JK, Wetzels JF
Abstract
Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid-resistant nephrotic syndrome in children and adults. Although FSGS is considered a podocyte disease, the aetiology is diverse. In recent years, many inheritable genetic forms of FSGS have been described, caused by mutations in proteins that are important for podocyte function. In the present commentary, we review these genetic causes of FSGS and describe their prevalence in familial and sporadic FSGS. In routine clinical practise, the decision to perform the costly DNA analysis should be based on the assessment if the results affect the care of the individual patient with respect to the evaluation of extra-renal manifestations, treatment decisions, transplantation and genetic counselling.
PMID: 22334613 [PubMed - as supplied by publisher]
Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis.
Nephrol Dial Transplant. 2012 Feb 8;
Authors: Bockmeyer CL, Kern DS, Forstmeier V, Lovric S, Modde F, Agustian PA, Steffens S, Birschmann I, Traeder J, Dämmrich ME, Schwarz A, Kreipe HH, Bröcker V, Becker JU
Abstract
BACKGROUND: Benign nephrosclerosis (bN) is the most prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of renal arterioles. Despite its high prevalence, very little is known about the contribution of arteriolar vascular smooth muscle cells (VSMCs) to bN. We examined classical and novel candidate markers of the normal contractile and the pro-fibrotic secretory phenotype of VSMCs in arterioles in bN.METHODS: Sixty-three renal tissue specimens with bN and eight control specimens were examined by immunohistochemistry for the contractile markers caldesmon, alpha-smooth muscle actin (alpha-SMA), JunB, smoothelin and the secretory marker S100A4 and by double stains for caldesmon or smoothelin with S100A4.RESULTS: Smoothelin immunostaining showed an inverse correlation with hyalinosis and fibrosis scores, while S100A4 correlated with fibrosis scores only. Neither caldesmon, alpha-SMA nor JunB correlated with hyalinosis or fibrosis scores. Cells in the arteriolar wall were exclusively positive either for caldesmon/smoothelin or S100A4.CONCLUSIONS: This is the first systematic analysis of VSMC differentiation in bN. The results suggest that smoothelin is the most sensitive marker for the contractile phenotype and that S100A4 could be a novel marker for the secretory phenotype in vivo. The other markers did not seem to differentiate these phenotypes in bN. Thus, VSMC phenotype markers should be defined in the context of the vessel segment and disease under examination. S100A4 could not only be a marker of pro-fibrotic secretory VSMCs in bN but also an important mediator of arteriolar fibrosis.
PMID: 22319217 [PubMed - as supplied by publisher]
Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients.
Nephrol Dial Transplant. 2012 Feb 8;
Authors: Minutolo R, Conte G, Cianciaruso B, Bellizzi V, Camocardi A, De Paola L, De Nicola L
Abstract
BACKGROUND: Lower responsiveness to erythropoiesis-stimulating agents (ESA-R) predicts cardiovascular (CV) events. Whether ESA-R also affects the risk of end-stage renal disease (ESRD) is unknown.METHODS: We evaluated ESA-R in 194 consecutive chronic kidney disease (CKD) patients, regularly seen in outpatient nephrology clinics, who started erythropoiesis-stimulating agent (ESA) therapy between 2002-06. Exclusion criteria were causes of anaemia other than CKD or recent transfusion. ESA-R was calculated as (Hb(1) – Hb(0))/time/ESA dose (g/dL/month/10 μg/week of ESA). Patients were classified, from lower to higher tertile of ESA-R, as poor, intermediate and good responders. Time to ESRD was the primary outcome.RESULTS: Age was 64 ± 16 years, 48% were male, 34% had diabetes and 32% had CV disease, glomerular filtration rate (GFR) 24 ± 13 mL/min/1.73 m(2) and proteinuria 0.6 g/dL (interquartile range 0.2-1.9). First ESA dose was 23.7 ± 10.8 μg/week; haemoglobin (Hb) increased from 9.9 ± 0.8 g/dL to 11.0 ± 1.2 g/dL at first control, obtained after 1.4 ± 0.4 months. These changes corresponded to an ESA-R of 0.37 ± 0.38 g/dL/month/10 μg/week of ESA and tertiles limits were 0.17 and 0.47. Poor responders were younger and had lower GFR and higher proteinuria than intermediate and good responders. During the first 6 months of ESA therapy, poor responders showed lower Hb levels and sustained longer periods of Hb level <11 g/dL. During follow-up (median 3.0 years), 99 patients reached ESRD. At multivariable Cox’s analysis, poor responsiveness was associated with higher risk of ESRD (hazard ratio 2.49, 95% confidence interval 1.28-4.84).CONCLUSION: ESA-R predicts renal prognosis in CKD patients followed in nephrology practice, where ESRD is the predominant outcome and ESA is commonly used at low dose.
PMID: 22319218 [PubMed - as supplied by publisher]
Vasopressin release is enhanced by the Hemocontrol biofeedback system and could contribute to better haemodynamic stability during haemodialysis.
Nephrol Dial Transplant. 2012 Feb 7;
Authors: Ettema EM, Kuipers J, Groen H, Kema IP, Westerhuis R, de Jong PE, Franssen CF
Abstract
BACKGROUND: Haemodialysis with the Hemocontrol biofeedback system (HHD) is associated with improved haemodynamic stability compared with standard haemodialysis (HD) (SHD). Although the beneficial effect of HHD on haemodynamic stability is generally explained by its effect on blood volume, we questioned whether additional factors could play a role. Since HHD is associated with higher initial dialysate sodium concentrations and ultrafiltration (UF) rate, we studied whether the beneficial effect of HHD on haemodynamic stability may be explained by an increased release of the vasoconstrictor arginine vasopressin (AVP).METHODS: Fifteen chronic dialysis patients underwent SHD and HHD in random order. All other treatment factors were identical and patients served as their own control. Plasma levels of AVP were measured pre-dialysis, at 30 and 60 min intra-dialysis and, next, hourly until completion of the dialysis session.RESULTS: Plasma AVP levels did not change significantly during SHD, whereas AVP levels rose significantly within 30 min after the start of HHD (P < 0.01). AVP levels were significantly higher at 30 and 60 min of HHD in comparison with SHD (P < 0.05). Dialysis hypotension occurred significantly less frequent during HHD than during SHD (P < 0.05).CONCLUSIONS: HHD is associated with higher initial AVP levels compared with SHD. The enhanced release of the vasoconstrictor AVP with HHD could contribute to the lower frequency of dialysis hypotension by facilitating fluid removal during the first part of the dialysis session, permitting lower UF rates during the second half of the dialysis session.
PMID: 22323529 [PubMed - as supplied by publisher]
Low hydrogen sulphide and chronic kidney disease: a dangerous liaison.
Nephrol Dial Transplant. 2012 Feb;27(2):486-93
Authors: Perna AF, Ingrosso D
Abstract
Hydrogen sulphide, H(2)S, is a gaseous compound involved in a number of biological responses, e.g. blood pressure, vascular function and energy metabolism. In particular, H(2)S is able to lower blood pressure, protect from injury in models of ischaemia-reperfusion and induce a hypometabolic state. In chronic kidney disease (CKD), low plasma hydrogen sulphide levels have been established in humans and in animal models. The enzymes involved in its production are cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulphurtransferase. The mechanisms for H(2)S decrease in CKD are related to the reduced gene expression (demonstrated in uraemic patient blood cells) and decreased protein levels (in tissues such as liver, kidney, brain in a CKD rat model). In the present Nephrol Dial Transplant issue, in fact, Aminzadeh and Vaziri document that the alterations in this pathway complicate the uraemic state and are linked to CKD progression. They furnish a time frame in CKD and record enzyme tissue distribution. It remains to be established if low H(2)S is causally linked to CKD progression and if interventions aimed to restore the status quo ante are able to modify this picture.
Fewer pre-emptive renal transplantations and more rejections in immigrant children compared to native Dutch and Belgian children.
Nephrol Dial Transplant. 2012 Feb 9;
Authors: Tromp WF, Cransberg K, van der Lee JH, Bouts AH, Collard L, Van Damme-Lombaerts R, Godefroid N, Van Hoeck KJ, Koster-Kamphuis L, Lilien MR, Raes A, Ranguelov N, Groothoff JW
Abstract
BACKGROUND: In the Netherlands and Belgium, an increasing number of children who have end-stage renal disease (ESRD) are of non-Western origin. We analysed renal transplantation practices and outcome for immigrant ESRD children as compared to native children in both countries.METHODS: All Dutch and Belgian children aged <19 years who received their first renal transplantation between 1 September 2007 and 1 January 2011 were included. Therapy characteristics and outcomes were registered prospectively on a 3-monthly basis. Immigrants were defined as children of whom one or both parents had been born outside Western European countries. Multivariable Cox regression analysis was used to quantify the hazard ratio for acute rejection.RESULTS: One hundred and nineteen first renal transplant recipients were included, of which 41 (34%) were immigrants. Median [range] follow-up time of transplantation was 18 [2-28] months. Compared to native children, immigrants had pre-emptive transplantations (15 versus 32%, P = 0.040) and transplantations with a kidney from a living donor less often (24 versus 59%, P < 0.001). Survival analysis in 96 children with at least 3 months of follow-up showed an increased risk for acute rejection in immigrants adjusted for donor source, duration of dialysis and number of HLA mismatches on the DR locus [hazard ratio (95% confidence interval) 2.5 (1.1-5.9)].CONCLUSIONS: Immigrant children receive fewer pre-emptive and living donor transplantations compared to native children. After transplantation, immigrant children are at higher risk for acute rejection irrespective of the mode of transplantation.
PMID: 22323533 [PubMed - as supplied by publisher]
BACKGROUND: In peritoneal dialysis (PD), the peritoneal membrane exhibits structural and functional changes following continuous exposure to the non-physiological peritoneal dialysis fluid (PDF). In this study, we examined the effect of PDF on peritoneal adipose tissue in a diabetic milieu.METHODS: Six-week-old db/db mice and their non-diabetic littermates (db/m) were subjected to uninephrectomy. All animals then received intra-abdominal infusion of lactated Ringer’s solution (Ringer) or 1.5% glucose-containing PDF (Dianeal) twice daily. Mice were sacrificed 4 weeks later. Parietal and visceral adipose tissues were harvested for examining gene and protein expression of adiponectin, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, tumor necrosis factor alpha (TNF-α), transforming growth factor beta and interleukin 6 (IL-6). Expression of TNF-α and F4/80+ macrophage accumulation in adipose tissues was assessed by immunohistochemical staining. Modulation of leptin synthesis and leptin receptors expression and the relevant signaling pathways were also determined by quantitative reverse transcription-polymerase chain reaction, immunoblotting or enzyme-linked immunosorbent assay.RESULTS: Compared to Ringer infusion, Dianeal infusion significantly increased serum leptin but decreased adiponectin in db/db mice. Increased expression of leptin, TNF-α and IL-6 was observed in visceral but not in parietal adipose tissue. Dianeal infusion also increased F4/80+ macrophage accumulation and enhanced the expression of pro-inflammatory cytokines including IL-6 and TNF-α in the visceral adipose tissue. Compared to db/m mice, infusion with Dianeal exhibited a more deleterious effect on db/db mice, characterized by an upregulation of short-form leptin receptor ObRa and activation of the mitogen-activated protein kinase signaling pathway.CONCLUSION: In conclusion, PD-induced hyperleptinemia amplifies the inflammatory response of adipose tissue through short-form leptin receptor when the long-form isotype is defective.
PMID: 22287654 [PubMed - as supplied by publisher]
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