C-reactive protein, cardiovascular risk, and renal disease in a remote Australian Aboriginal community

Rates of cardiovascular and renal disease in Australian Aboriginal communities are high, but we do not know the contribution of inflammation to these diseases in this setting. In the present study, we sought to examine the distribution of C-reactive protein (CRP) and other markers of inflammation and their relationships with cardiovascular risk markers and renal disease in a remote Australian Aboriginal community. The study included 237 adults (58% of the adult population) in a remote Aboriginal community in the Northern Territory of Australia. Main outcome measures were CRP, fibrinogen and lgG concentrations, blood pressure (BP), presence of diabetes, lipids, albuminuria, seropositivity to three common micro-organisms, as well as carotid intima-media thickness (IMT). Serum concentrations of CRP [7 (5-13) mg/l; median (inter-quartile range)] were markedly increased and were significantly correlated with fibrinogen and lgG concentrations and inversely correlated with serum albumin concentration. Higher CRP concentrations were associated with lgG seropositivity to Helicobacter pylori and Chlamydia pneumoniae and higher lgG titre for cytomegalovirus. Higher CRP concentrations were associated with the following: the 45-54-year age group, female subjects, the presence of skin sores, higher body mass index, waist circumference, BP, glycated haemoglobin and greater albuminuria. CRP concentrations increased with the number of cardiovascular risk factors, carotid IMT and albuminuria independently of other risk factors. These CRP concentrations were markedly higher than described in other community settings and are probably related, in a large part, to chronic and repeated infections. Their association with markers of cardiovascular risk and renal disease are compatible with the high rates of cardiovascular and renal disease in this community, and provide more evidence of strong links between these conditions, through a shared background of infection/inflammation. This suggests that a strong focus on prevention and management of infections will be important in reducing these conditions, in addition to interventions directed at more traditional risk factors.

Angiotensin II facilitates autoregulation in the perfused mouse kidney: An optimized in vitro model for assessment of renal vascular and tubular function

Background and Aims: We have optimized the isolated perfused mouse kidney (IPMK) model for studying renal vascular and tubular function in vitro using 24-28 g C57BL6J mice; the wild type controls for many transgenic mice. Methods and Results: Buffer composition was optimized for bovine serum albumin concentration (BSA). The effect of adding erythrocytes on renal function and morphology was assessed. Autoregulation was investigated during stepped increases in perfusion pressure. Perfusion for 60 min at 90-110 mmHg with Krebs bicarbonate buffer containing 5.5% BSA, and amino acids produced functional parameters within the in vivo range. Erythrocytes increased renal vascular resistance (3.8 +/- 0.2 vs 2.4 +/- 0.1 mL/min.mmHg, P < 0.05), enhanced sodium reabsorption (FENa = 0.3 +/- 0.08 vs 1.5 +/- 0.7%, P < 0.05), produced equivalent glomerular filtration rates (GFR; 364 +/- 38 vs 400 +/- 9 muL/min per gkw) and reduced distal tubular cell injury in the inner stripe (5.8 +/- 1.7 vs 23.7 +/- 3.1%, P < 0.001) compared to cell free perfusion. The IPMK was responsive to vasoconstrictor (angiotensin II, EC50 100 pM) and vasodilator (methacholine, EC50 75 nM) mediators and showed partial autoregulation of perfusate flow under control conditions over 65-85 mmHg; autoregulatory index (ARI) of 0.66 +/- 0.11. Angiotensin II (100 pM) extended this range (to 65-120 mmHg) and enhanced efficiency (ARI 0.21 +/- 0.02, P < 0.05). Angiotensin II facilitation was antagonized by methacholine (ARI 0.76 +/- 0.08) and papaverine (ARI 0.91 +/- 0.13). Conclusion: The IPMK model is useful for studying renal physiology and pathophysiology without systemic neurohormonal influences.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses

Purpose: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.Methods: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.Results: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05). Arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039), venous reaction time was linked to creatinine clearance (p=0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p<0.001 and p=0.003 respectively) and the dilatation amplitude (p=0.038 and p=0.048 respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017), vWf was linked to the maximum constriction response (p=0.016), and creatinine clearance to the baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022). Conclusions: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

The Genetic Landscape of Renal Complications in Type 1 Diabetes

Diabetes is the leading cause of end stage renal disease. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2,843 subjects, we estimated that the heritability of diabetic kidney disease was 35% ( p=6x10-3 ). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index ( p=2.2×10-5) and the risk of type 2 diabetes (p=6.1x10-4 ) were associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation ( p=1.1×10-4 ). Pathway analysis implicated ascorbate and aldarate metabolism ( p=9×10-6), and pentose and glucuronate interconversions ( p=3×10-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.  

Squamous cell carcinoma of the renal pelvis with stones and inferior vena cava infiltration. Case report

We report a rare case of a 50 year old man with renal squamous cell carcinoma (SCC) who first came to our attention with renal colic and fever not responding to antibiotic or analgesic treatment. He had a long history of kidney stones, but had not undergone any imaging in the last 5 years. Physical examination revealed tenderness and a palpable mass in the right flank and lumbar region. A whole body CT scan was performed, revealing an 11 cm mass in the right kidney infiltrating the inferior vena cava. There were areas of calcification within the mass and multiple stones within the renal pelvis. The tumor was considered unsuitable for resection according to radiological and clinical criteria. The mass was biopsied percutaneously under CT guidance and histological examination revealed squamous cell carcinoma of the renal pelvis. The patient was treated with neoadjuvant chemotherapy and embolization of the renal artery. He died one month after diagnosis. To our knowledge this is the second reported case in the world of renal SCC infiltrating the inferior vena cava and with kidney stones.

One-stage laparoscopic procedure for a patient with bilateral colorectal tumours and renal carcinoma

We describe a case of a patient with synchronous bilateral colorectal tumours and renal carcinoma who underwent one-stage laparoscopic surgery procedure with right transperitoneal nefrectomy, right hemicolectomy and sigmoidectomy. One-stage laparoscopic procedure can be used safely and successfully for a patient with multiple primary tumours.

Suspecting Renal Artery Thrombosis

Renal artery thrombosis is a threatening clinical diagnosis, in which renal infarction may occur. Often misdiagnosed, for mimicking other common diseases, it should be considered in persistent flank pain to improve care and reduce morbidity. We review a case of a healthy, 57 year-old woman with renal artery thrombosis mimicking pyelonephritis and renal calculus obstruction, highlighting features of this clinical condition. An accurate diagnosis is essential for optimal management and prompts treatment, which still remains to be defined.

Dose-Adjusted Beta-Lactam Antibiotic-Induced Encephalopathy in a Patient with End-Stage Renal Impairment: A Case Report

Introduction: Despite adherence to current guidelines regarding dose adjustment and drug-level monitoring, beta-lactam-induced encephalopathy can still occur in the setting of chronic renal impairment. Case Report: We report what we believe is the first case of piperacillin- and tazobactam-induced encephalopathy in a patient with pre-existing cefepime-induced encephalopathy in the context of end-stage kidney disease despite adequate dose adjustment for renal impairment.

Epigastric Pain in Acute Renal Infarction: The Forgotten Presentation

Epigastric pain is a manifestation of several medical and surgical conditions. However, when persistent epigastric pain is associated with microscopic or frank haematuria and elevated lactate dehydrogenase (LDH), especially in patients with increased risk of thromboembolic events, acute renal infarction (ARI) should be considered. We report the case of a 77-year-old male patient who presented with sudden persistent epigastric pain and elevated LDH who was found to have atrial fibrillation. The patient was diagnosed with ARI. ARI is not usually a typical differential diagnosis in patients with persistent epigastric pain and elevated LDH in whom the risk of thromboembolic events is high. Thus, physicians should perform a contrast-enhanced CT scan as early as possible to rule out or confirm renal infarction.

Índice del perfil del donante renal (KDPI) como factor pronóstico del trasplante

La enfermedad renal crónica ha aumentado a nivel mundial y nacional, mientras que el número de donantes viene en descenso, y los pacientes en lista de espera aumentan. Los donantes cadavéricos son una opción para estos pacientes, y han sido utilizados en últimos años para aumentar los órganos disponibles. La evaluación de la calidad de estos es importante para optimizar su uso. Estudio analítico tipo cohorte retrospectiva, cálculo de KDPI en donantes cadavéricos, seguimiento función renal creatinina sérica 1 mes, 3 meses, 6 meses y un año. Correlación supervivencia del injerto, función renal, KDPI y EPTS. Análisis de supervivencia y regresión logística con variables del donante, receptor y acto quirúrgico.

Association Between Prehypertension, Metabolic And Inflammatory Markers, Decreased Adiponectin And Enhanced Insulinemia In Obese Subjects.

Obesity is associated with development of the cardiorenal metabolic syndrome, which is a constellation of risk factors, such as insulin resistance, inflammatory response, dyslipidemia, and high blood pressure that predispose affected individuals to well-characterized medical conditions such as diabetes, cardiovascular and kidney chronic disease. The study was designed to establish relationship between metabolic and inflammatory disorder, renal sodium retention and enhanced blood pressure in a group of obese subjects compared with age-matched, lean volunteers. The study was performed after 14 h overnight fast after and before OGTT in 13 lean (BMI 22.92 ± 2.03 kg/m(2)) and, 27 obese (BMI 36.15 ± 3.84 kg/m(2)) volunteers. Assessment of HOMA-IR and QUICKI index were calculated and circulating concentrations of TNF-α, IL-6 and C-reactive protein, measured by immunoassay. THE STUDY SHOWS THAT A HYPERINSULINEMIC (HI: 10.85 ± 4.09 μg/ml) subgroup of well-characterized metabolic syndrome bearers-obese subjects show higher glycemic and elevated blood pressure levels when compared to lean and normoinsulinemic (NI: 5.51 ± 1.18 μg/ml, P < 0.027) subjects. Here, the combination of hyperinsulinemia, higher HOMA-IR (HI: 2.19 ± 0.70 (n = 12) vs. LS: 0.83 ± 0.23 (n = 12) and NI: 0.98 ± 0.22 (n = 15), P < 0.0001) associated with lower QUICKI in HI obese when compared with LS and NI volunteers (P < 0.0001), suggests the occurrence of insulin resistance and a defect in insulin-stimulated peripheral action. Otherwise, the adiponectin measured in basal period was significantly enhanced in NI subjects when compared to HI groups (P < 0.04). The report also showed a similar insulin-mediated reduction of post-proximal urinary sodium excretion in lean (LS: 9.41 ± 0.68% vs. 6.38 ± 0.92%, P = 0.086), and normoinsulinemic (NI: 8.41 ± 0.72% vs. 5.66 ± 0.53%, P = 0.0025) and hyperinsulinemic obese subjects (HI: 8.82 ± 0.98% vs. 6.32 ± 0.67%, P = 0.0264), after oral glucose load, despite elevated insulinemic levels in hyperinsulinemic obeses. In conclusion, this study highlights the importance of adiponectin levels and dysfunctional inflammatory modulation associated with hyperinsulinemia and peripheral insulin resistance, high blood pressure, and renal dysfunction in a particular subgroup of obeses.

Urinary Tract Infection In Renal Transplant Recipients: Incidence, Risk Factors, And Impact On Graft Function.

Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival.

Long-term Results Of Anderson-hynes Pyeloplasty In Children: How Long Follow-up Is Necessary?

Purpose After a successful pyeloplasty at 3 to 6 months, the question remains whether children need a long follow-up. Methods The medical charts of patients with long-term follow-up (> 5 years), who underwent dismembered pyeloplasty for uretero-pelvic junction obstruction (UPJO) from May 1998 to May 2007, excluding those with bilateral UPJO, solitary kidney, associated vesicoureteral reflux or other abnormalities, and inconclusive renogram due to poor renal function, were retrospectively reviewed. Ultrasonography, differential renal function (DRF, DMSA), and renal drainage on diuretic renography (diethylene-triamine-pentaacetate technetium-99 or DTPA-Tc99) were performed at 3 and 6 months every year. Results Complete data were available for 28 consecutive patients (28 renal unities) with 2 months to 12 years (mean age, 2.4 years) at surgery, of whom 21 (75%) were boys, 17 diagnosed prenatally (61%) and 18 unities (64.3%) were left, with median follow-up of 10.7 years. Images were graded according to the Society for Fetal Urology grading system: Grade III in 11 (49%) and grade IV in 17 (61%). All cases presented > 10% DRF (DMSA) and obstructed DTPA-Tc99. The T1/2 (the half-time of drainage) less than 20 minutes at 3 months was found in 21 cases (75%) and less than 25 minutes in 7 cases (25%). Renal function and patency were maintained during follow-up for all units with 8% maximum fluctuation of DRF. One index case (3.6%) of renal function deterioration presented DRF fluctuation > 8% at 3 months (from 23 to 32%) and progressive hydronephrosis and indeterminate DTPA at 6 months. Conclusions Satisfactory diuretic renogram at 3 to 6 months after pyeloplasty with maintained renal function and stable hydronephrosis suggests no need for further follow-up and indicates no functional loss with time. More than 8% DRF fluctuation might be a significant cutoff for further intervention aiming nephron preservation.

Influence Of Cyclosporine On The Occurrence Of Nephrotoxicity After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review.

Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: bone marrow transplantation OR stem cell transplantation OR grafting, bone marrow AND cyclosporine OR cyclosporin OR risk factors AND acute kidney injury OR acute kidney injuries OR acute renal failure OR acute renal failures OR nephrotoxicity. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.