Oxidative stress, inflammation, and peritoneal dialysis: A molecular biology approach.

The key role of oxidative stress (OxSt) and inflammation for the induction of cardiovascular disease, the leading cause of excess morbidity/mortality in chronic kidney disease and dialysis patients, is known and both the activations of NADPH oxidase and RhoA/Rho kinase (ROCK) pathway are pivotal for their effects. While specific hemodialysis procedures, such as hemodiafiltration with on-line reinfusion of ultrafiltrate and/or the use of vitamin E-coated dialyzers, are beneficial for OxSt and inflammation, studies in peritoneal dialysis (PD) are instead scarce and results seem not favorable. In nine patients under PD OxSt in terms of mononuclear cell protein level of p22phox (Western blot), subunit of NADPH oxidase, essential for the generation of OxSt, and MYPT-1 phosphorylation state (Western blot), a marker of ROCK activity, have been measured at the beginning and after 3 and 6 months of PD. Blood levels of interleukin 6 (IL-6), ferritin, and albumin have been considered for evaluating the inflammatory state. p22phox protein expression, MYPT-1-phosphorylation, and ferritin level were increased both at baseline vs healthy subjects (P = .02, P < .0001, P = .004, respectively) and vs baseline after 3 and 6 months of peritoneal dialysis (P = .007, P < .001, P = .004, respectively). Albumin was lower after 6 months of PD (P = .0014). IL-6 was increased at baseline vs reference values and remained unchanged at 3 and 6 months. OxSt and inflammation increase during PD confirming via molecular biology approach a report at biochemical level. To improve OxSt state in PD, a multitarget approach is necessary. It might include the use of more physiologic pH, low glucose degradation products, low lactate and iso-osmolar PD solutions, patients' strict glycemic control, optimal volume management, and antioxidant administration, such as N-acetylcysteine.

Efficacy of weekly administration of cholecalciferol on parathyroid hormone in stable kidney-transplanted patients with CKD stage 1-3.

Objectives: Kidney transplant (KTx) recipients frequently have deficient or insufficient levels of serum vitamin D. Few studies have investigated the effect of cholecalciferol in these patients. We evaluated the efficacy of weekly cholecalciferol administration on parathyroid hormone (PTH) levels in stable KTx patients with chronic kidney disease stage 1-3. Methods: In this retrospective cohort study, 48 stable KTx recipients (37 males, 11 females, aged 52 ± 11 years and 26 months post-transplantation) were treated weekly with oral cholecalciferol (7500-8750 IU) for 12 months and compared to 44 untreated age- and gender-matched recipients. Changes in levels of PTH, 25(OH) vitamin D (25[OH]D), serum calcium, phosphate, creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline, 6 and 12 months. Results: At baseline, clinical characteristics were similar between treated and untreated patients. Considering the entire cohort, 87 (94.6%) were deficient in vitamin D and 64 (69.6%) had PTH ≥130 pg/mL. Serum calcium, phosphate, creatinine and eGFR did not differ between groups over the follow-up period. However, 25(OH)D levels were significantly higher at both 6 (63.5 vs. 30.3 nmol/L, p < 0.001) and 12 months (69.4 vs. 30 nmol/L, p < 0.001) in treated vs. untreated patients, corresponding with a significant reduction in PTH at both 6 (112 vs. 161 pg/mL) and 12 months (109 vs. 154 pg/mL) in treated vs. untreated patients, respectively (p < 0.001 for both). Conclusions: Weekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.

Pathophysiology of Post Transplant Hypertension in Kidney Transplant: Focus on Calcineurin Inhibitors Induced Oxidative Stress and Renal Sodium Retention and Implications with RhoA/Rho Kinase Pathway.

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the treatment of hypertension with different antihypertensive drugs inducing a comparable blood pressure reduction but different effects for example on oxidative stress and oxidative stress related proteins and/or Rho kinase and sodium retention, could be helpful for the choice of the antihypertensive treatment in these patients which takes advantage from effects of these drugs beyond blood pressure reduction.

In Patients with Chronic Kidney Disease Short Term Blood Pressure Variability is Associated with the Presence and Severity of Sleep Disorders.

BACKGROUND/AIMS: In chronic kidney disease (CKD) patients blood pressure variability (BPV) is associated with poor outcome. Sleep disturbances alter BP profiles in hypertensives but their influence on BPV in CKD patients is unknown. We screened a cohort of CKD/ESRD patients to investigate whether sleep quality impacts on BPV. METHODS: Consecutive CKD patients' sleep quality was assessed using validated questionnaires (Epworth Sleepiness Scale-ESS); International Restless legs scale-IRLS; Functional Outcomes of Sleep Questionnaire-FOSQ: Insomnia Severity Index-ISI; STOP-Bang). All patients underwent ambulatory blood pressure measurement. RESULTS: 104 out of 143 enrolled patients (78.32% stage-3 CKD; 10.49% Stage-4; 11.19% Stage-5; 6.99% ESRD-under dialysis) completed all the questionnaires. 95.8% were hypertensives, 70% were non-dippers and 27.8% had resistant hypertension. STOP-Bang>4 proved sleep disorders in 84.84% of patients. Patients with IRLS>10 had greater diastolic nocturnal standard deviation (DNSD) and a trend (p=0.05) for systolic nocturnal SD (SNSD). Patients with ISI>14 had greater SNSD and in 28.8% FOSQ showed severely impaired sleep quality. Their systolic nocturnal BPV was significantly greater. ISI was independently associated with SNSD. FOSQ and diastolic nocturnal BPV were negatively correlated at the bivariate analysis and FOSQ independently predicts systolic nocturnal BPV at multivariate regression analysis. CONCLUSIONS: In CKD patients impaired sleep quality increases BPV, might contribute to their disease progression and worsen prognosis. Searching for sleep problems in CKD patients could help planning their treatment of sleep problems contributing to CV risk reduction. Our data provide the rationale working hypothesis for the need of studies with larger number of patients aimed to demonstrate improved outcome of CKD progression and CV risk with the treatment also of sleep disorders.

Hepatitis C virus infection in end-stage renal disease and kidney transplantation.

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV-positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct-acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV-negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV-related liver disease.

Comparison of cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV quantiferon gamma interferon-releasing assays in assessing risk of CMV infection in kidney transplant recipients.

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R+) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D+/R-). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P<0.05). During the antiviral prophylaxis, all 20 D+/R- KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.

Outcomes of endovascular aneurysm repair on renal function compared with open repair.

OBJECTIVE: Recent studies have shown that progressive renal dysfunction may develop in patients after endovascular aneurysm repair (EVAR). Data are conflicting about the effect of EVAR on renal function compared with open repair (OR). The purpose of this study was to compare the effects of EVAR, both with transrenal fixation (TRF) and infrarenal fixation (IRF), vs OR on renal function detected with renal perfusion scintigraphy (RPS). METHODS: A prospective study was carried out from January 2003 to December 2007. Exclusion criteria included factors that could influence post-procedural renal function as: preoperative creatinine clearance level <65 mL/min for men and 60 mL/min for women, renal artery stenosis >60%, renal accessory artery planned to be covered by the endograft, single functioning kidney, hemodialysis, and kidney transplant. To evaluate renal function, an RPS was performed preoperatively, at 30 days, at 6 and 12 months, and then yearly. The glomerular filtration rate (GFR) was estimated with the Gates method. RESULTS: During the study period, 403 patients were enrolled; 243 (60%) had OR and 160 (40%) EVAR; among these, 83 (51%) had a TRF and 77 (48%) an IRF; 55 patients were excluded from the study. No statistical differences were observed between groups for demographics and risk factors. Statistically significant differences emerged between OR and EVAR for early postoperative death (4% vs 0%; P = .01). Follow-up ranged from 54 to 126 months (mean, 76 months) for OR and from 54 to 124 months (mean, 74 months) for EVAR (P = NS). Kaplan-Meier analysis survival rate at 9 years was 70% for OR and 58% for EVAR with a risk of secondary procedure of 9% and 34%, respectively (P < .0001). A deterioration of the GFR was observed during the follow-up in both groups with a decrease after 9 years of 11% in the EVAR group and 3% in the OR group respective to baseline (P < .001). A remarkable difference emerged on renal function between EVAR patients who required a secondary procedure compared with the other EVAR patients (P < .005). No significant differences emerged between TFR and IRF for GFR decline during the follow-up period. CONCLUSIONS: After EVAR, there is a continuous decline in renal function with respect to OR, regardless of fixation level and independently of pre-existing renal insufficiency. The risk of GFR impairment after EVAR should be taken into consideration in selecting patients with preoperative renal insufficiency.

High chronic nephropathy detection yield in CKD subjects identified by the combination of albuminuria and estimated GFR.

BACKGROUND AND OBJECTIVES: Epidemiological studies have shown that the burden of chronic kidney disease (CKD) is huge. CKD is a non-specific diagnosis, however, and it is hard to say which renal disorders comprise the body of CKD diagnosed on the strength of the combination of albuminuria and estimated glomerular filtration rate (eGFR) in epidemiological studies, or just how efficient such studies are in detecting chronic nephropathies. METHODS: The INCIPE study identified 524 CKD cases (using the K/DOQI definition based on albuminuria and eGFR) in a random sample of 4000 Italians >40 years old, 262 of whom were randomly chosen to be investigated in order to confirm their CKD and complete a diagnostic workup. We a priori defined diagnostic algorithms for 14 renal conditions based on personal family history, medical records, urine tests, kidney ultrasound with colour-Doppler and other tests. RESULTS: Among the subjects whose CKD was confirmed, a diagnosis of chronic nephropathy was reached in 68% of cases recognized as having either a specific (38%) or an undetermined (30%) kidney disease. Almost 50% of subjects with a specific chronic nephropathy had a diabetic or vascular renal disease. Abnormalities consistent with a chronic nephropathy were found in 50, 68, 70 and 100% of subjects with CKD Stages 1, 2, 3 and 4, respectively. Lone low eGFR and lone microalbuminuria were observed in 20 and 12%, respectively. CONCLUSION: In Caucasians >40 years old with a confirmed CKD condition, (i) an impressive 68% of subjects have an underlying chronic nephropathy, so eGFR and albuminuria are very efficient in detecting renal diseases; (ii) in 32%, the only disclosed renal abnormalities were a glomerular filtration rate <60 mL/min/1.73 m(2) or microalbuminuria; follow-up studies are needed to clarify whether these abnormalities do really identify a chronic nephropathy or just a cardiovascular risk condition.

Urinary peptides as a diagnostic tool for renal failure detected by matrix-assisted laser desorption/ionisation mass spectrometry: an evaluation of their clinical significance.

The development of new analytical methodologies related to the proteome for the evaluation of renal physiology and pathology is surely of wide interest for physicians, giving them new tools for monitoring complications associated with diabetes, such as end-stage renal disease. In the present study, the clinical significance of the urinary abundance of two peptides, SGSVIDQSRVLNLGPITR (the uromodulin precursor, m/z 1912) and IGPHypGPHypGLMGPP [present in the collagen-α-5(IV) chain precursor, m/z 1219], detected by matrix- assisted laser desorption/ionisation mass spectrometry (MALDI/MS) in microalbuminuric or nephropathic diabetic patients and in non-diabetic nephropathic patients was evaluated. A progressive increase in the abundance of the ion at m/z 1219 and a decrease in the abundance of the ion at m/z 1912 have been found in diabetic microalbuminuric, diabetic-nephropathic and nephropathic patients. Linear correlations are present between serum creatinine values and the abundances of the ions at m/z 1219 (positive correlation, r=0.3645, P<0.0001) and at m/z 1912 (negative correlation, r=-0.3053, P<0.0005). Correlations between the MALDI data and the estimated glomerular filtration rate were also found, while relationships with urinary albumin excretion were found only in sub-sets of patients. Analysis of receiver operating characteristic curves showed a sensitivity up to 96% and a specificity of up to 84% for the two ionic species, or their ratio, for distinguishing diabetic patients with different degrees of nephropathy from healthy subjects, proving that the urinary abundance of the two peptides at m/z 1219 and m/z 1912, determined with MALDI/MS, may be considered as a possible diagnostic tool for the determination of progression toward renal failure, also with the aim of monitoring kidney function, in diabetic patients.

Evaluation of cytomegalovirus (CMV)-specific T cell immune reconstitution revealed that baseline antiviral immunity, prophylaxis, or preemptive therapy but not antithymocyte globulin treatment contribute to CMV-specific T cell reconstitution in kidney transplant recipients.

BACKGROUND: The ultimate goal of organ transplantation is the reestablishment of organ function and the restoration of a solid immunity to prevent the assault of potentially deadly pathogens. T cell immunity is crucial in controlling cytomegalovirus (CMV) infection. It is still unknown how preexisting antiviral T cell levels, prophylaxis, or preemptive antiviral strategies and pharmacological conditioning affect immune reconstitution. METHODS: Seventy preemptively treated CMV-seropositive recipients, 13 prophylaxis-treated CMV-seronegative recipients of seropositive donor transplants, 2 seropositive recipients of seronegative donor kidneys, and 27 pretransplant subjects were enrolled in a cross-sectional study and analyzed for CMV viremia (DNAemia) and CMV-specific T cell response (interferon-gamma enzyme-linked immunospot assay) before transplantation and at 30, 60, 90, 180, and 360 days after transplantation. RESULTS: CMV-seropositive transplant recipients displayed a progressive but heterogeneous pattern of immune reconstitution starting from day 60 after transplantation. CMV-seronegative recipients did not mount a detectable T cell response throughout the prophylaxis regimen. A single episode of CMV viremia (CMV copy number, 7000-170,000 copies/mL) was sufficient to prime a protective T cell immune response in CMV-seronegative recipients. Antithymocyte globulin treatment did not significantly affect CMV-specific T cell response. CONCLUSIONS: Baseline immunity, antiviral therapy but not antithymocyte globulin treatments profoundly influence T cell reconstitution in kidney transplant recipients.

Comparison between creatinine-based equations for estimating total creatinine clearance in peritoneal dialysis: a multicentre study.

BACKGROUND: It is crucial to assess the adequacy of peritoneal dialysis (PD) because of its influence on patient outcome. Collecting dialysate and urine for 24 h can be rather troublesome, so a simple and inexpensive alternative method for rapidly evaluating adequacy in PD would be very useful. Our study aimed to assess the performance of 12 different creatinine (Cr)-based equations commonly used to estimate GFR in predicting total Cr clearance (totCrCL) in PD. METHODS: Four Italian dialysis centres enrolled 355 PD patients with 2916 fluid collections. To rank the equations, their accuracy (median absolute percentage error, MAPE), precision (root mean square error, RMSE), agreement (k statistics), sensitivity and specificity (area under ROC curves, AUC, where x = 1 - specificity and y = sensitivity) were calculated with reference to the measured totCrCL. RESULTS: The Gates, Virga and 4-MDRD equations showed the best global performance as concerns accuracy (MAPE = 14.1, 16.3, 15.9% respectively), precision (RMSE = 13.2, 13.3, 13.4), agreement (k = 0.425, 0.440, 0.375), sensitivity and specificity (AUC = 0.825, 0.826, 0.820), while the Cockcroft-Gault formula revealed a rather poor reliability. CONCLUSIONS: Fluid collection remains the gold standard for assessing PD adequacy. Our study ascertained how 12 Cr-based equations performed in estimating totCrCL in PD patients with a view to enabling the most accurate and precise among them to be chosen for use in approximately assessing totCrCL.

Early activation of fibrogenesis in transplanted kidneys: a study on serial renal biopsies.

BACKGROUND/AIMS: In kidney transplants, the renin-angiotensin system (RAS) is involved in systemic and local changes that may induce fibrosis. Our aim was to use gene expression and immunohistochemical analysis to investigate the RAS and several factors involved in the fibrogenic cascade in allograft biopsies. METHODS: We considered 43 donor biopsies (T0), 18 biopsies obtained for diagnostic purposes (Td) and 24 protocol biopsies (Tp) taken 2 months after transplantation in patients with stable renal function. Morphometric alpha SMA and TGF beta 1 analysis, and Masson's Trichrome staining were performed. mRNA levels of angiotensinogen, renin, ACE, AT1-R, AT2-R, TGF beta 1, BMP-7, Coll III, fibronectin and alpha SMA were analyzed by real-time RT/PCR. MDRD a year after the transplant was also considered. RESULTS: Significantly higher levels of AT1-R and alpha SMA transcripts were found in Tp than in T0. Regression analysis showed significant TGF beta 1-independent positive correlations between RAS and matrix components in T0 and Tp, but more evident in Tp, where a positive correlation between TGF beta 1 and Masson's Trichrome stained areas was also seen. CONCLUSION: Our results suggest that RAS and TGF beta 1-related fibrogenic loops are activated as early as 2 months after kidney transplantation.

Georg Philip Nenter and medicine "by notes" in the 18th century.

Even though it is true that the medical historiography of the 18th century is lacking in great scientific personalities, it is equally true that the entire century is characterized by continuous efforts to encapsulate the medical area of knowledge, acquired until then, in precise and systematic outlines, to serve the academic teaching of the subject of medicine. Georg Philip Nenter, a pupil of Georg Ernst Stahl and a professor of medicine in the University of Strasburg, could not help being influenced by that atmosphere. He added though, in our opinion, a touch of remarkable modernity. In fact his volume Fundamenta medicinae teoretico-pratica (Venice, 1735) is a wonderful collection of the notes taken during his lectures. The description of various diseases - renal diseases in particular - maintains a very systematic development of the subject through various chapters (definition, clinical manifestations, differential diagnosis, prognosis, treatment and examples of specific prescriptions), as if students were being addressed.

Primary IgA nephropathy is more severe in TGF-beta1 high secretor patients.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-beta1 has a key role in fibrogenesis and the progression of renal damage. Its production is under genetic control. METHODS: We recruited 105 Italian biopsy-proven IgAN patients for genotyping for the TGF-beta1 C-509T, T869C (COD 10) and G915C (COD 25) polymorphisms; 200 healthy blood donors were used as normal controls. Glomerular and interstitial mRNA levels of TGF-beta1 were assessed by real-time PCR in 34 patients to seek relationships with clinical, renal histopathological features and outcome. RESULTS: The genotype distributions in the IgAN population were not statistically different from the controls. The COD 10 TT genotype was associated with more severe histological damage as assessed by Lee's classification (CC 50%, CT 39.6% and TT 17.2% were graded as mild; CC 35.7%, CT 43.7% and TT 44.8% as moderate, and CC 14.3%, CT 16.7% and TT 37.9% as severe [p=0.0049]) and with severe interstitial infiltrates (CC 10.4%, CT 35.2% and TT 54.2% [p=0.03]). A higher interstitial immunodeposition was observed for TGF-beta1, collagen IV and alpha-SMA in patients with the COD 10 T allele (p=0.045, p=0.049, p=0.032, respectively). The T allele was associated with significantly higher TGF-beta1 mRNA levels in the interstitium (TT+CT vs. CC: 0.52 +/- 0.16 vs. 0.18 +/- 0.10 copies/mL, respectively; p=0.000). The T allele was also associated with higher mRNA levels in glomeruli, though the difference was not statistically significant. Finally, the T allele was significantly associated with a worse prognosis, the end points being reached by 40% of TT+CT and 32% of CC patients (p=0.009). CONCLUSIONS: In primary IgA nephropathy, the T allele of the TGF-beta1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-beta1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.

[Follow-up of the kidney donor]. / Il follow-up nel donatore.

Kidney transplant from a living donor is known to be the best renal replacement therapy. While not as common as in northern Europe and the USA, living donor transplants are on the rise in Italy. Although there is a large body of evidence in the literature about the safety of the surgical procedure, the risk of long-term complications for the donor has not been clearly defined because of the lack of studies with adequate follow-up and a sufficient number of subjects involved. The main questions concern the development of chronic kidney disease in the donor, expressed as a GFR decline or the presence of microalbuminuria. The physiopathological basis of GFR decline and proteinuria development may differ from the model of nephropathy in patients with two kidneys, and this could involve prognostic differences too, particularly with regard to the cardiovascular risk. Detailed and prolonged follow-up programs are needed to monitor and, if necessary, treat long-term complications in kidney donors.

Nonenzymatically glycated lipoprotein ApoA-I in plasma of diabetic and nephropathic patients.

ApoA-I, which constitutes 70% of the apolipoprotein content of high-density lipoproteins, acts as an acceptor for the transfer of phospholipids and free cholesterol from peripheral tissues and transports cholesterol in the liver and other tissue for excretion and steroidogenesis. In order to verify its possible structural alteration in pathological states, plasma samples from healthy, diabetic, and nephropathic subjects have been analyzed by two-dimensional gel electrophoresis. By this approach, clear differences among the three classes of subjects become evident and, in the case of diabetic and nephropathic patients, intense spots are present. The matrix-assisted laser desorption/ionization mass spectrometry analysis of their digestion products shows that an overexpression of unglycated and glycated ApoA-I is present in both pathological states, reasonably affecting the efficiency in cholesterol transport.

On the search for glycated lipoprotein ApoA-I in the plasma of diabetic and nephropathic patients.

The analysis of plasma samples from healthy, diabetic and nephropathic subjects was carried out by 2D gel electrophoresis. This approach shows clear differences among the three classes of subjects. In the case of diabetic and nephropathic patients intense spots appear. Their enzymatic digestion followed by matrix assisted laser desorption ionization/mass spectrometry (MALDI/MS) analysis shows that an overexpression of unglycated and glycated ApoA-I is present in both pathological states. Interestingly, this trend is also observed for the retinol-binding protein (RBP). The data obtained can be relevant to assess possible risks associated either with the glycation level of ApoA-I or with the overexpression of RBP. In fact, in the former case possibly a different functionality of the glycated protein is to be expected, reflecting a different efficiency in cholesterol transport. In the latter case, the increase of RBP level can be related to the overweight of the diabetic subjects under investigation: it is known that obesity leads to RBP overexpression. In the case of nephropathic patients, the RBP level increases in parallel with serum creatinin.

Low vitamin K1 intake in haemodialysis patients.

BACKGROUND & AIMS: Vitamin K acts as a coenzyme in the γ-carboxylation of vitamin K-dependent proteins, including coagulation factors, osteocalcin, matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6) protein. Osteocalcin is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification. GAS6 activity prevents the apoptosis of vascular smooth muscle cells. Few data on vitamin K intake in chronic kidney disease patients and no data in patients on a Mediterranean diet are available. In the present study, we evaluate the dietary intake of vitamin K1 in a cohort of patients undergoing haemodialysis. METHODS: In this multi-centre controlled observational study, data were collected from 91 patients aged >18 years on dialysis treatment for at least 12 months and from 85 age-matched control subjects with normal renal function. Participants completed a food journal of seven consecutive days for the estimation of dietary intakes of macro- and micro-nutrients (minerals and vitamins). RESULTS: Compared to controls, dialysis patients had a significant lower total energy intake, along with a lower dietary intake of proteins, fats, carbohydrates, fibres, and of all the examined minerals (Ca, P, Fe, Na, K, Zn, Cu, and Mg). With the exception of vitamin B12, vitamins intake followed a similar pattern, with a lower intake in vitamin A, B1, B2, C, D, E, folates, K1 and PP. These finding were confirmed also when normalized for total energy intake or for body weight. In respect to the adequate intakes recommended in the literature, the prevalence of a deficient vitamin K intake was very high (70-90%) and roughly double than in controls. Multivariate logistic model identified vitamin A and iron intake as predictors of vitamin K deficiency. CONCLUSIONS: Haemodialysis patients had a significantly low intake in vitamin K1, which could contribute to increase the risk of bone fractures and vascular calcifications. Since the deficiency of vitamin K intake seems to be remarkable, dietary counselling to HD patients should also address the adequacy of vitamin K dietary intake and bioavailability. Whether diets with higher amounts of vitamin K1 or vitamin K supplementation can improve clinical outcomes in dialysis patients remains to be demonstrated.

Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins.

Matrix Gla protein (MGP) and bone Gla protein (BGP) are two vitamin K-dependent proteins (VKDPs) involved in the regulation of vascular calcification (VC). We carried out a secondary analysis of the VIKI study to evaluate associations between drug consumption and VKDP levels in 387 hemodialyzed patients. The VIKI study assessed the prevalence of vitamin K deficiency in hemodialysis patients. We evaluated drug consumption, determined BGP and MGP levels, and verified the presence of any vertebral fractures (VF) and VC by spine radiographs. Total BGP levels were twice as high with calcimimetics versus no calcimimetics (290 vs. 158.5 mcg/L, p < 0.0001) and 69 % higher with vitamin D analogs (268 vs. 159 mcg/L, p < 0.0001). Total MGP was 19 % higher with calcimimetics (21.5 vs. 18.1 mcg/L, p = 0.04) and 54 % higher with calcium acetate (27.9 vs. 18.1 mcg/L, p = 0.003); no difference was found with vitamin D analogs (21.1 vs. 18.3 mcg/L, p = 0.43). Median Total BGP level was 29 % lower in patients with ≥1 VF (151 vs. 213 mcg/L, p = 0.0091) and 36 % lower in patients with VC (164 vs. 262.1 mcg/L, p = 0.0003). In non-survivors, median BGP and MGP were lower, but only for MGP this difference reached the statistical significance (152 vs. 191 mcg/L, p = 0.20 and 15.0 vs. 19.7 mcg/L, p = 0.02, respectively). Pending studies on vitamin K supplementation, calcimimetics, and vitamin D analogs may play a role in preserving vitamin K-dependent protein activity, thus contributing to bone and vascular health in CKD patients.