Role of Inherited Thrombophilia Risk Factors in Patients with CKD-5 Receiving Haemodialysis.

BACKGROUND: The inherited thrombophilic mutations of the factor V gene (FVG1691A Leiden-FVL), prothrombin gene (PTG20210A), and the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) are risk factors for thromboembolic events and are related to the pathogenesis of vascular diseases. OBJECTIVES: The main objective of this study was to explore the role of these factors in the pathogenesis of chronic kidney disease (CKD) and survival of patients with CKD-5 receiving haemodialysis. METHODS: A cohort of 395 patients with CKD-5 on haemodialysis, from 6 dialysis units in Crete, Greece were recruited based on their medical records and were followed for 5 years. We collected data on CKD-5 aetiology, thrombophilic gene expression, vascular access thrombosis, time of death, and causes of death. RESULTS: The mutated genes just as prevalent in patients with CKD-5 as they were in a control group with no renal disease (p > 0.05). FVL heterozygosity was significantly more prevalent (11.4 vs. 5.7%; p = 0.036) in patients presented with CKD of unknown aetiology, compared to CKD secondary to known aetiologies. The survival of patients with CKD-5 receiving haemodialysis was not affected by the presence of any thrombophilic mutation. This held true for the whole cohort and for the cohort that included only lethal vascular events. Most patients with MTHFR C677T heterozygosity, and all patients with MTHFR C677T homozygosity, died from vascular events during the follow-up period. CONCLUSION: The FVL mutation may act as a risk factor for CKD. This study increases our understanding of molecular mechanisms in the pathogenesis of CKD of unknown aetiology. Τhe presence of thrombophilic mutations did not affect the overall survival of patients with CKD-5. This finding probably reflects the effect of medical care on patient outcomes.

Selecting the optimal peritoneal dialysis catheter.

As the incidence of end stage renal disease increases across the globe, so too do the survival rates of peritoneal dialysis patients. It is notable though, that peritoneal dialysis utilization does not follow at the same pace, attributable into the high technique failure rates, mainly due to peritoneal catheter dysfunction. A new systematic review and meta-analysis by Hagen et al. reveals that the use of straight catheters may improve outcomes and technique survival.

Human TTRV30M localization within podocytes in a transgenic mouse model of transthyretin related amyloidosis: does the environment play a role?

Transthyretin related amyloidosis is a nosological entity that leads to disability, diminished quality of life, all stages of chronic kidney disease and eventually death. Podocytes are polarized, highly differentiated epithelial cells important for proper nephron function. In the present study we investigated whether deposited TTRVal30Met (TTRV30M) molecules could be localized within podocytes in situ under the effect of different housing conditions (i.e. specific pathogen free [SPF] vs. non-SPF). Murine renal glomeruli from human TTRV30M (hTTRV30M) transgenic mice were examined via direct and indirect immunofluorescence techniques for the presence of hTTRV30M, murine serum amyloid P, activated caspase-3 and NPHS1. Association strength and amount of colocalization for NPHS1-hTTRV30M, NPHS1-activated caspase-3, hTTRV30M-murine serum amyloid P were estimated. Localization of hTTRV30M in podocytes was demonstrated by immuno-electron microscopy. Renal hTTRV30M gene and NPHS1 gene expression levels were estimated. Non-SPF transgenic mice showed increased glomerular hTTRV30M deposition compared to their SPF counterparts. Furthermore increased podocytic localization of hTTRV30M was noticed in non-SPF mice. Glomerular caspase-3 activation was increased only in the non SPF housing conditions. Podocytic caspase-3 activation was increased in SPF and in non-SPF transgenic mice when compared to non transgenic controls. Environmental conditions influence glomerular deposition and podocytic localization of hTTRV30M. In this context increased caspase-3 activation occurred.

Rapamycin ameliorates proteinuria and restores nephrin and podocin expression in experimental membranous nephropathy.

OBJECTIVE: Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated. METHODS: Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week. RESULTS: Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression. CONCLUSIONS: Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin.

Rapamycin induced ultrastructural and molecular alterations in glomerular podocytes in healthy mice.

BACKGROUND: In the normal kidney, rapamycin is considered to be non-nephrotoxic. In the present study, we investigated whether rapamycin is indeed non-nephrotoxic by examining the ultrastructural and molecular alterations of podocytes in healthy mice. METHODS: Balb/c mice were given three different intraperitoneal doses of rapamycin for 1 week (dose model)-low-dose group: 1 mg/kg/day, intermediate-dose (ID) group: 1.5 mg/kg/day and high-dose (HD) group: 3 mg/kg/day; four mice in each group. An ID of rapamycin was also given for three different periods (time model): 1, 4 and 8 weeks; four mice were in each group. Mice treated with dimethyl sulphoxide served as controls. Body weight was measured weekly. Renal function was assessed by serum creatinine at the time of sacrifice. For estimation of albuminuria, 24-h urine collections were performed before treatment and weekly thereafter. Glomerular content of nephrin, podocin, Akt and Ser473-phospho-Akt was estimated by western blot and immunofluorescence. Nephrin and podocin messenger RNA (mRNA) were measured by real-time polymerase chain reaction. Mean podocyte foot process width (FPW) was measured by electron microscopy. RESULTS: Urine albumin levels increased in the HD and 4-week groups. Renal function was modestly deteriorated in the HD group. The mean FPW increased in a dose-dependant manner at Week 1, further deteriorated at Week 4 and finally improved at Week 8. Nephrin and podocin mRNA levels showed a significant decrease at Week 1 and were restored at Week 4 and 8. Nephrin and podocin protein levels were reduced at Week 4 and recovered at Week 8. Ser473-phospho-Akt significantly increased in all rapamycin-treated groups. CONCLUSIONS: Rapamycin induced significant ultrastructural and molecular alterations in podocytes in association with albuminuria. These alterations happened early during treatment and they tended to improve over an 8-week treatment period.

Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients.

BACKGROUND: In the general population, accumulating data support a link between low testosterone levels and mortality by all causes, but especially by cardiovascular disease (CVD). Also, accelerated arterial stiffness has been recognized as an important cardiovascular risk factor. Here, we explored the association between testosterone levels and risk of death in male haemodialysis (HD) patients, whose arterial system is characterized by generalized stiffening. METHODS: In this three-centre prospective observational study, 111 male HD patients after completion of baseline assessment, including measurement of male sex hormones and pulse wave velocity (PWV), were followed up for CVD and all-cause mortality. RESULTS: Of the 111 patients studied, 54 were found with and 57 without testosterone deficiency, defined as testosterone levels <8 nmol/L. During a median follow-up period of 37 months, 49 deaths occurred, 28 (57%) of which were caused by CVD. Testosterone deficiency patients had increased CVD and all-cause mortality {crude hazard ratio: 3.14 [95% confidence interval (CI), 1.21-8.16] and 3.09 (95% CI, 1.53-6.25), respectively}, even after adjustment for age, body mass index, serum albumin and C-reactive protein, prevalent CVD and HD vintage. The association of testosterone with CVD mortality, but not with all-cause mortality, was lost after adjusting for PWV, an index of arterial stiffness. Testosterone levels were inversely related to PWV (r = -0.441; P < 0.001). CONCLUSION: We showed that testosterone deficiency in male HD patients is associated with increased CVD and all-cause mortality and that increased arterial stiffness may be a possible mechanism explaining this association.

The PI3K/Akt/mTOR pathway is activated in murine lupus nephritis and downregulated by rapamycin.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor, rapamycin, has been shown to inhibit the progression of murine lupus nephritis by virtue of its potent immunosuppressive properties. The phosphoinositol-3-kinase (PI3K)/Akt pathway is a major upstream activator of mTOR and has been implicated in the propagation of cancer and autoimmunity. However, the activation status of the PI3K/Akt/mTOR pathway in lupus nephritis has not been studied so far. METHODS: In NZBW/F1 female mice, we examined the glomerular expression of Akt and mTOR by immunofluorescence and western blot. We also searched for specific phosphorylations of these kinases known to ensue during activation of the PI3K/Akt/mTOR pathway. In parallel, we examined the therapeutic role of rapamycin either before or after the development of overt lupus nephritis. RESULTS: We found that in untreated mice, as opposed to healthy controls, Akt and mTOR were over-expressed and phosphorylated at key activating residues. Rapamycin prolonged survival, maintained normal renal function, normalized proteinuria, restored nephrin and podocin levels, reduced anti-dsDNA titres, ameliorated histological lesions, and reduced Akt and mTOR glomerular expression activation. CONCLUSIONS: These results suggest that: (i) the PI3K/Akt/mTOR pathway is upregulated in murine lupus nephritis, thus justifying treatment with rapamycin; (ii) rapamycin not only blocks mTOR but also negatively regulates the PI3K/Akt/mTOR pathway; and (iii) rapamycin is an effective treatment of murine lupus nephritis. Examination of the PI3K/Akt/mTOR pathway may offer new insights into the pathogenesis of lupus nephritis in humans and may lead to more individualized and less toxic treatment.

Intense immunostaining of heat shock protein 70 within renal interstitium associates with long-term renal survival in an ANCA-associated vasculitis cohort.

In anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) genetic predisposition, ANCA autoantibodies, neutrophil extracellular traps (NETs), complement activation, and toll-like receptor signaling are implicated in AAV pathogenesis. Heat shock proteins (HSPs), a highly conserved group of small-sized molecular chaperones, take part in protein folding during cellular stress. Although HSPs were initially observed intracellularly, it has been shown that they can be secreted in the extracellular space and modulate the immune response in various autoimmune diseases including AAV. The scope of the present study is to investigate the role of heat shock protein 60 (HSP60) and 70 (HSP70) in the long renal effects in an ANCA vasculitis cohort. In this cohort of ANCA-associated vasculitis, 29 patients were followed up over 20 years. At diagnosis, immunohistochemistry was performed for HSP60 and HSP70 within the various nephron compartments. Higher renal HSP60 expression was associated with increased interstitial inflammatory infiltrates at diagnosis, while HSP70 expression was associated with a greater extent of interstitial fibrosis at diagnosis. Notably, intense tissue expression of HSP70 at the time of biopsy was associated with a worsened kidney survival. Renal HSP70 expression was associated with poor renal outcomes during long-term follow-up. This finding may indicate a role of HSPs in renal disease progression in ANCA vasculitis. Further validating studies are needed to verify a causative association between HSP70 expression and renal outcomes in ANCA-associated vasculitis.

Biopsy-proven resolution of renal light-chain deposition disease after autologous stem cell transplantation.

Light-chain deposition disease (LCDD) is caused by an underlying clonal plasma cell dyscrasia in which monoclonal immunoglobulin light chains (LCs) are deposited in tissues, resulting in varying degrees of organ dysfunction. Autologous stem cell transplantation (ASCT) has been reported to stabilize renal function in patients with LCDD, but currently, no evidence of histopathologic resolution of LC deposition after ASCT exists. We present a patient, with severe renal dysfunction due to LCDD, who was treated with high-dose melphalan and ASCT that resulted in a significant and extended period of improved renal function. Four years after the initial improvement, the patient developed nephrotic range proteinuria, without any evidence of relapse of the plasma cell dyscrasia. At that time, a repeat renal biopsy showed complete resolution of LC depositions and development of extensive glomerulosclerosis, thus explaining proteinuria. To the best of our knowledge, this is the first report of a biopsy-proven resolution of renal LCDD following ASCT. A timely application of ASCT should be considered in LCDD to prevent deterioration of renal function in the long run.

Prognostic utility of impedance cardiography measurements in elderly hemodialysis patients with coronary artery disease.

AIM: We evaluated the utility of impedance cardiography (IC) in elderly hemodialysis (HD) patients with coronary artery disease (CAD). PATIENTS AND METHODS: Seventy-five HD patients (30 with CAD) participated. IC cardiac output (ICCO), systemic vascular resistance and pulse pressure (PP) were calculated at baseline, and 30 and 180 days after study entry. ICCO was compared to echocardiography cardiac output (ECO). Relationships of IC measurements and cardiovascular mortality were assessed. Patients were followed up for 6 years after study entry or until death due to cardiovascular events. RESULTS: ICCO and ECO were strongly correlated (r = 0.94, p < 0.001). ICCO correlated inversely with PP (r = -0.61; p < 0.001). Thirty fatal cardiovascular events were recorded. Using the bayesian' information criterion, multivariate Cox regression models revealed that increased PP and New York Heart Association (NYHA) class as well as decreased diastolic blood pressure (DBP) were predictors of cardiovascular mortality. Having a DBP <60 mm Hg (adjusted for NYHA) yielded a hazard ratio of 2.8 (95% confidence interval = 1.2-6.7). CONCLUSION: IC accurately estimates the hemodynamic status in HD patients with CAD. Deterioration of cardiovascular performance expressed by decreased DBP values, adjusted for NYHA, may help to predict outcome.

Long-term complication rates and survival of peritoneal dialysis catheters: the role of percutaneous versus surgical placement.

Considerable controversy currently exists in the literature concerning the mode of catheter placement and its impact on the technical success of peritoneal dialysis (PD). We decided to compare the impact of the surgical versus the percutaneous insertion technique on peritoneal dialysis catheter (PDCs) complications and survival. Our study population comprised 152 patients in whom 170 PDCs were inserted between January 1990 and December 2007 at the main PD unit on the island of Crete. Eighty four catheters were surgically placed (S group) and 86 were placed percutaneously by nephrologists (N group). The total experience accumulated was 4997 patient-months. The overall complications did not differ between the two groups. Only early leakage was more frequent in N group than S group (10.3 versus 1.9 episodes per 1000 patient-months; p < 0.001). However, it was easily treated and did not constitute a cause of early catheter removal. Catheter survival was 91.1%, 80.7%, and 73.2%, in the S group versus 89.5%, 83.7%, and 83.7% for the N group at 1, 2, and 3 years, respectively (p = 0.2). Catheter survival has significantly increased over the last decade. Factors positively affecting PDC survival appeared to be the use of mupirocin for exit site care and the utilization of the coiled type of catheter, practices implemented mainly after 1999. Peritonitis-free survival and patient survival were not associated with the mode of placement, while in Cox regression analysis, were longer in patients treated with automated PD. The placement mode did not affect PD outcomes. Percutaneous implantation proved a safe, simple, low cost, immediately available method for PDC placement and helped to expand our PD program.

Percutaneous ethanol injection therapy: a surgery-sparing treatment for primary hyperparathyroidism.

OBJECTIVE: To describe our 3-year experience in the long-term efficacy and safety of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery for the management of patients with primary hyperparathyroidism (p-HPT). DESIGN: Prospective study with a mean follow-up of 19.6 +/- 10.6 months. PATIENTS: Our study population included 19 consecutive high risk patients with p-HPT, who met the criteria for surgery. MEASUREMENTS: Under ultrasonic guidance, ethanol (95%) was injected into parathyroid glands with a volume of >or= 0.15 cm(3). With the aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections were carried out, in an interval of 2 weeks, until normalization of iPTH was reached or until no residual blood supply was detected by ultrasound in the gland. Biochemical parameters were monitored throughout the study. RESULTS: At 6-month follow-up, normalization of iPTH levels (10-65 ng/l) was achieved in 11 (58%) patients (responders). Of the eight remaining patients (nonresponders), six patients had reduced (but not normalized) iPTH levels and two patients required parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19 patients (89.5%) became normocalcaemic (serum Ca 200 ng/l. The only complication was a transient dysphonia noticed in three patients. CONCLUSIONS: PEIT is a safe and effective nonsurgical treatment for patients with p-HPT, who are unsuitable for surgical intervention.

Renal artery stenting for atherosclerotic renal artery stenosis identified in patients with coronary artery disease: Does captopril renal scintigraphy predict outcomes?

The authors evaluated the effectiveness of percutaneous renal revascularization (PRR) with stenting for the treatment of atherosclerotic renal artery stenosis (ARAS) in patients with coronary artery disease and the usefulness of captopril renal scintigraphy for predicting clinical outcomes after PRR. Sixty-four consecutive patients, referred for evaluation of suspected ARAS, after coronary angiography, underwent baseline captopril renal scintigraphy followed by renal angiography. Forty-four patients (68.7%) were diagnosed with a significant ARAS≥ 60% and were treated with PRR plus medical therapy. Twenty-four months after PRR, 86.4% and 73.3% of patients showed a hypertension and renal benefit, respectively. Captopril renal scintigraphy positivity had moderate sensitivity and high specificity in predicting a hypertension and renal benefit. In patients with ARAS≥ 70%, the sensitivity and specificity were 100% for both a hypertension and renal benefit.PRR for ARAS conferred a substantial benefit in patients with a high coronary artery disease burden. Captopril renal scintigraphy was highly accurate in predicting clinical outcomes.

Preoperative Albuminuria and Intraoperative Chloride Load: Predictors of Acute Kidney Injury Following Major Abdominal Surgery.

BACKGROUND: Postoperative Acute Kidney Injury (AKI) is a common and serious complication associated with significant morbidity and mortality. While several pre- and intra-operative risk factors for AKI have been recognized in cardiac surgery patients, relatively few data are available regarding the incidence and risk factors for perioperative AKI in other surgical operations. The aim of the present study was to determine the risk factors for perioperative AKI in patients undergoing major abdominal surgery. METHODS: This was a prospective, observational study of patients undergoing major abdominal surgery in a tertiary care center. Postoperative AKI was diagnosed according to the Acute Kidney Injury Network criteria within 48 h after surgery. Patients with chronic kidney disease stage IV or V were excluded. Logistic regression analysis was used to evaluate the association between perioperative factors and the risk of developing postoperative AKI. RESULTS: Eleven out of 61 patients developed postoperative AKI. Four intra-operative variables were identified as predictors of AKI: intra-operative blood loss (p = 0.002), transfusion of fresh frozen plasma (p = 0.004) and red blood cells (p = 0.038), as well as high chloride load (p = 0.033, cut-off value > 500 mEq). Multivariate analysis demonstrated an independent association between AKI development and preoperative albuminuria, defined as a urinary Albumin to Creatinine ratio ≥ 30 mg·g-1 (OR = 6.88, 95% CI: 1.43⁻33.04, p = 0.016) as well as perioperative chloride load > 500 mEq (OR = 6.87, 95% CI: 1.46⁻32.4, p = 0.015). CONCLUSION: Preoperative albuminuria, as well as a high intraoperative chloride load, were identified as predictors of postoperative AKI in patients undergoing major abdominal surgery.

IgA nephropathy in Greece: data from the registry of the Hellenic Society of Nephrology.

BACKGROUND: Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A nephropathy (IgAN) and follow-up of at least 12 months. METHODS: Patients with normal renal function and proteinuria <1 g/24 h as well as those with serum creatinine (SCr) >2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr. RESULTS: The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients. CONCLUSION: The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.

Arterial stiffness alterations during hemodialysis: the role of dialysate calcium.

BACKGROUND/AIMS: We investigated the way dialysate calcium (dCa) level can influence arterial stiffness (AS), measured by stiffness index (SI), a surrogate of pulse wave velocity, and reflection index (RI), a measure of the amount of pulse wave reflection, derived by digital volume pulse (DVP). METHODS: Fourteen hemodialysis (HD) patients underwent two consecutive midweek 4-hour HD treatments in randomized order with a low dCa concentration of 1.25 mmol/l (LdCa) and a high dCa concentration of 1.75 mmol/l (HdCa), respectively. Before HD and at 1-hour intervals during the subsequent 4-hour HD sessions, SI and RI measurements were obtained from DVP contour analysis. Blood pressure (BP) and heart rate (HR) were measured after each measurement of AS. Ionized serum calcium (iCa) was measured before HD and at 120 and 240 min into the HD session. RESULTS: iCa increased and decreased by 15.3 and 5.4% in the HdCa and LdCa groups, respectively, at the end of HD. SI and RI increased by 5.7 and 6% in the HdCa group, respectively, whereas they remained unchanged in the LdCa group. The treatment effect and the time x treatment effect were significant for both indices (ANOVA). BP and HR changes did not differ between treatments. CONCLUSION: Contrary to LdCa, HdCa treatment induced a BP-independent, significant increase in measured AS parameters. In the long run, HD with LdCa, by reducing the incidence of HD-induced hypercalcemia, may have a beneficial role in minimizing the cardiovascular risk related to the intermittent, intradialytic increase in AS, inherent in the chronic use of HdCa.

Acute renal failure, translocational hyponatremia and hyperkalemia following intravenous immunoglobulin therapy.

BACKGROUND/AIMS: Intravenous immunoglobulin (IVIG) therapy has been associated with renal adverse effects and electrolyte disturbances. METHODS: We retrospectively evaluated a cohort of 66 unselected patients with idiopathic thrombocytopenic purpura, who received 140 courses of IVIG therapy. Acute renal failure (ARF), hyponatremia and hyperkalemia, as potential complications of IVIG therapy, were assessed from 100 IVIG courses with sufficient data for analysis. RESULTS: Thirteen out of 100 (13%) IVIG courses in 10 (15%) patients were complicated with ARF. Risk factors included advanced age, pre-existing renal impairment, use of diuretics and the presence of diabetes mellitus. All patients recovered renal function 1-2 weeks after IVIG infusion. Serum sodium (sNa) fell by 5.7 and 2.7 mmol/l (p < 0.01) in patients with and without ARF, respectively. Correspondingly, serum potassium increased by 0.7 and 0.23 mmol/l (p < 0.01). There was a strong inverse correlation (r = -0.308; p < 0.01) between changes in sNa and creatinine. Changes in serum potassium could be independently predicted by changes in both sNa and creatinine (R(2) = 0.11; p < 0.01). These data suggested that both hyponatremia and hyperkalemia were (a) due to the translocational effect of the osmotic load of sucrose, and (b) largely depended on the extent of IVIG nephropathy. CONCLUSION: In our series, ARF attributable to IVIG therapy, although not rare, was usually mild and fully reversible. High-risk patients were more susceptible to IVIG-related renal complications. Translocational hyponatremia and hyperkalemia following IVIG therapy, although unimportant in patients with normal renal function, may be of clinical significance in patients with severely compromised renal function, resulting in impaired sucrose excretion.

Can a left internal jugular catheter be used in the hemodialysis of a patient with persistent left superior vena cava?

A patient with a persistent left superior vena cava (PLSVC) was incidentally diagnosed after positioning of a dual lumen catheter for hemodialysis into the left internal jugular vein. Although PLSVC is a relatively rare condition, it is the most common congenital anomaly of thoracic venous circulation. It represents the persistence of the left horn of the embryonic sinus venosus, which normally involutes during embryogenesis to become the coronary sinus. The existence of a PLSVC can cause a significant diagnostic dilemma during catheterization of the left internal jugular vein, pertaining to the positioning of the catheter. It may also be associated with significant clinical implications such as systemic embolization, provocation of arrhythmia, and thrombosis of the vessel. The safety of such catheterization has not been adequately evaluated due to the rarity of this condition. We believe that a diagnostic workup including blood gas analysis, echocardiography, and computed tomography is necessary to confirm a right atrial drainage and a patent innominate vein as prerequisites to maintain the catheter in position.

Parathyromatosis and the challenge of treatment.

Parathyromatosis, consisting of hyperfunctioning parathyroid tissues scattered throughout the neck, is a rare cause of recurrent hyperparathyroidism after parathyroidectomy. Medical management of patients with parathyromatosis usually is ineffective. Repeated surgery often is necessary, but generally is unsuccessful. We describe a case of parathyromatosis as a cause for recurrent hyperparathyroidism. A 32-year-old woman with a history of end-stage renal disease on hemodialysis therapy for 13 years developed secondary hyperparathyroidism requiring subtotal parathyroidectomy. Three years later, hyperparathyroidism relapsed. A technetium Tc 99m-sestamibi scan showed remnant parathyroid tissue on the left inferior thyroid lobe. Percutaneous ethanol infusion therapy failed to suppress parathormone excess, and neck exploration was performed. Histological examination of pathological lesions confirmed the diagnosis of parathyromatosis. Despite extended resection of multiple parathyroid nodules, symptoms worsened, leading progressively to severe morbidity. Imaging studies at this point showed widespread hyperfunctioning parathyroid tissue within the neck. The patient refused a third operation; thus, we resorted to coadministration of paricalcitol, a less hypercalcemic vitamin D analogue, and ibandronate, a new-generation bisphosphonate. Parathormone secretion was suppressed partially with this regimen, even at the expense of hypercalcemia and hyperphosphatemia. Sustained normalization of hormone levels and normocalcemia were accomplished only after substitution of ibandronate for the calcimimetic agent cinacalcet. The question of whether calcimimetics may maximize the chance of complete cure of parathyromatosis, especially when surgical treatment fails or is not feasible, remains to be answered by future studies.

Androgen deficiency and endothelial dysfunction in men with end-stage kidney disease receiving maintenance hemodialysis.

OBJECTIVES AND METHODS: Two thirds of men with end-stage kidney disease (ESKD) have serum testosterone levels in the hypogonadal range. We examined if low serum testosterone levels were correlated with measures of endothelial dysfunction in ESKD. Bilateral common carotid artery (CCA) intima-media thickness (IMT) and atherosclerotic plaque occurrence, left ventricular mass index, flow- (FMD) and nitrate-mediated vasodilatation (NMD) of the brachial artery were determined by ultrasound imaging in 100 nondiabetic men with ESKD (50 men exhibited androgen deficiency; serum testosterone concentrations <300 ng/dl). RESULTS: Left-ventricular mass index, CCA diameter, CCA-IMT and atherosclerotic plaque occurrence were all significantly increased in ESKD patients with androgen deficiency compared with patients without androgen deficiency (p < 0.05). Also, FMD and NMD measurements were significantly reduced in the former compared with the latter (p < 0.05). Testosterone levels were inversely correlated with age and duration of hemodialysis therapy (r = -0.44 and r = -0.55; p < 0.001). Testosterone levels were negatively correlated to CCA-IMT and atherosclerotic plaque occurrence in patients with androgen deficiency (r = -0.32, p < 0.003, and r = -0.23, p < 0.04, respectively). FMD and NMD measurements were positively correlated to total (r = 0.65 and r = 0.61; both p < 0.0001) and free (r = 0.52 and r = 0.48; both p < 0.001) testosterone levels in patients with low androgenicity. CONCLUSION: The present results indicated that ESKD patients with androgen deficiency had increased CCA-IMT, atherosclerotic plaque occurrence and reduced FMD and NMD compared with patients without androgen deficiency. Testosterone serum levels were negatively correlated to CCA-IMT and positively correlated to endothelium-dependent vasodilatation in ESKD patients with androgen deficiency.