Vascular Function in Chronic Kidney Disease and in Renovascular Disease

Cardiovascular mortality is 15 to 30 times higher in patients with chronic kidney disease than in the age-adjusted general population. Even minor renal dysfunction predicts cardiovascular events and death in the general population. In patients with atherosclerotic renovascular disease the annual cardiovascular event and death rate is even higher. The abnormalities in coronary and peripheral artery function in the different stages of chronic kidney disease and in renovascular disease are still poorly understood, nor have the cardiac effects of renal artery revascularization been well characterized, although considered to be beneficial. This study was conducted to characterize myocardial perfusion and peripheral endothelial function in patients with chronic kidney disease and in patients with atherosclerotic renovascular disease. Myocardial perfusion was measured with positron emission tomography (PET) and peripheral endothelial function with brachial artery flow-mediated dilatation. It has been suggested that the poor renal outcomes after the renal artery revascularization could be due to damage in the stenotic kidney parenchyma; especially the reduction in the microvascular density, changes mainly evident at the cortical level which controls almost 80% of the total renal blood flow. This study was also performed to measure the effect of renal artery stenosis revascularization on renal perfusion in patients with renovascular disease. In order to do that a PET-based method for quantification of renal perfusion was developed. The coronary flow reserve of patients with chronic kidney disease was similar to the coronary flow reserve of healthy controls. In renovascular disease the coronary flow reserve was, however, markedly reduced. Flow-mediated dilatation of brachial artery was decreased in patients with chronic kidney disease compared to healthy controls, and even more so in patients with renovascular disease. After renal artery stenosis revascularization, coronary vascular function and renal perfusion did not improve in patients with atherosclerotic renovascular disease, but in patients with bilateral renal artery stenosis, flow-mediated dilatation improved. Chronic kidney disease does not significantly affect coronary vascular function. On the contrary, coronary vascular function was severely deteriorated in patients with atherosclerotic renovascular disease, possibly because of diffuse coronary artery disease and/or diffuse microvascular disease. The peripheral endothelial function was disturbed in patients with chronic kidney disease and even more so in patient with atherosclerotic renovascular disease. Renal artery stenosis dilatation does not seem to offer any benefits over medical treatment in patients with renovascular disease, since revascularization does not improve coronary vascular function or renal perfusion.Vaskulaarifunktio kroonisessa munuaisten vajaatoiminnassa ja renovaskulaaritaudissa Kuolleisuus sydän- ja verisuonisairauksiin kroonista munuaisten vajaatoimintaa sairastavilla potilailla on 15 – 30 -kertainen taustaväestöön verrattuna. On osoitettu, että jo lieväkin munuaisten vajaatoiminta ennustaa sydän- ja verisuonitauti tapahtumia ja kuolleisuutta väestössä. Ateroskleroottista renovaskulaaritautia sairastavilla vuotuinen kuolleisuus sydän- ja verisuonisairauksiin on vielä suurempi. Sepelvaltimoiden ja ääreisverenkierron toiminnasta on vain vähän tutkimustietoa niin munuaisten vajaatoimintaa kuin renovaskulaaritautiakin sairastavilla. Myöskään munuaisvaltimoahtauman laajentamisen aiheuttamia muutoksia sydämen ja ääreisverenkierron toimintaan ei ole juuri tutkittu. Tämän tutkimuksen tarkoituksena oli ensisijaisesti selvittää sydämen verenvirtausta, sepelvaltimoiden toiminnallista kapasiteettia eli sepelvaltimoiden virtausreserviä ja ääreisverenkierron toiminnan muutoksia niin kroonista munuaisten vajaatoimintaa sairastavilla kuin ateroskleroottista renovaskulaaritautia sairastavilla potilailla. Tutkimusmenetelminä käytettiin positroniemissiotomografiaa (PET) sydämen verenvirtauksen määrittämiseksi sekä ultraäänitutkimusta perifeerisen ääreisverenkierron toiminnan tutkimiseksi. Viime vuosina on arveltu, että kliinisten tutkimusten huonot tulokset munuaisvaltimoahtauman laajennuksen jälkeisesti liittyisivät munuaisten pienten verisuonten toiminnallisiin ja rakenteellisiin muutoksiin munuaisvaltimoahtauman vaikutuksesta. Muutoksia on havaittu erityisesti munuaisten kuorikerroksessa, joka käyttää noin 80 % munuaiseen ohjautuvasta verenvirtauksesta. Tutkimuksen toisena tavoitteena oli mitata mahdollisia muutoksia munuaisten verenvirtauksessa munuaisvaltimoahtauman laajentamisen jälkeisesti. Tätä varten kehitimme PET -metodin munuaisten verenvirtauksen määrittämiseksi. Sepelvaltimoiden virtausreservi kroonista munuaisten vajaatoimintaa sairastavilla ei eronnut tilastollisesti merkitsevästi terveiden verrokeiden virtausreservistä. Sen sijaan renovaskulaaritautipotilaiden virtausreservi oli vaikea-asteisesti huonontunut. Olkavarsivaltimon laajenemiskapasitetti oli huonontunut munuaisten vajaatoimintaa sairastavilla terveisiin verrattuna ja renovaskulaaritautipotilailla vielä enemmän. Munuaisvaltimoahtauman laajentamisen jälkeisesti renovaskulaaritautipotilaiden sepelvaltimoiden funktiossa tai munuaisten verenvirtauksessa ei havaittu parantumista. Kuitenkin molemminpuolisesta munuaisvaltimoahtaumasta kärsivillä ääreisverenkierron toiminta parantui tilastollisesti merkitsevästi toimenpiteen jälkeen. Johtopäätöksinä voidaan todeta, että munuaisten vajaatoiminta sinällään ei näyttäisi merkitsevästi huonontavan sepelvaltimoiden virtausreserviä. Sen sijaan renovaskulaaritautia sairastavilla virtausreservi on huono, todennäköisesti joko subkliinisen sepelvaltimotaudin ja/tai mikrovaskulaaritaudin aiheuttamana. Ääreisverenkierron toiminta sen sijaan oli huonontunut molemmissa potilasryhmissä, renovaskulaaritautipotilailla vielä enemmän. Munuaisvaltimoahtauman laajentaminen ei näytä tarjoavan hyötyä lääkehoitoon verrattuna, sillä toimenpiteen jälkeisesti ei havaittu muutoksia sydämen virtausreservissä sen paremmin kuin munuaisten verenvirtauksessakaan.Siirretty Doriast

Uusi strategia vaikean kroonisen munuaistaudin hoidonohjaukseen

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Acute kidney injury in group A streptococcal bacteraemia: incidence, outcome and predictive value of C-reactive protein

Background: A ubiquitous human pathogen, Streptococcus pyogenes (Group A Streptococcus, GAS) causes infections from mild pharyngitis to severe septic infections. Acute kidney injury (AKI) is a condition of prompt decline of renal function. The aim of the present study was to report the incidence and outcome of AKI in GAS bacteraemia and to evaluate the diagnostic value of serum C-reactive protein as an indicator of AKI.Methods: All adult patients with GAS bacteraemia treated at Turku University Hospital from 2007 to 2018 were identified and their patient records were scrutinised.Results: Of 195 included patients, 38 (19.5%) had AKI stage 1, 20 (10.3%) AKI stage 2 and 26 (13.3%) AKI stage 3 and 111 (56.9%) did not have AKI. The adjusted seven-day mortality was significantly higher in AKI stages 2 and 3 compared to the non-AKI group (15% and 19% vs. 3.6%; p = .046 and .006, respectively). Of the survivors, 95.8% met the criteria of renal recovery at discharge. The higher the AKI stage, the higher was the mean serum CRP level on admission. The optimal cut-off for CRP to identify patients with AKI stage 2 or 3 was ≥244 mg/l (sensitivity 82.6% and specificity 75.8%).Conclusions: AKI is common in patients with GAS bacteraemia and the severity of AKI correlates with the CRP level on admission. The mortality of patients with GAS bacteraemia and AKI is significantly higher than of patients without AKI. Most survivors, however, show renal recovery.Key MessageAKI is common in group A Streptococcal bacteraemia and increases mortality compared to bacteraemia alone. However, renal recovery is also common. A high CRP level on admission correlates significantly positively with the degree of severity of AKI.</p

Association between bone mineral metabolism and vascular calcification in end-stage renal disease

Background: Development of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism.Methods: Thirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 - L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score.Results: This study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured.Conclusions: The results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished.</p

Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients

BackgroundThe diagnosis of renal osteodystrophy is challenging. Bone biopsy is the gold standard, but it is invasive and limited to one site of the skeleton. The ability of biomarkers to estimate the underlying bone pathology is limited. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging technique that allows assessment of regional bone turnover at clinically relevant sites. The hypothesis of this study was, that 18F-NaF PET correlates with bone histomorphometry in dialysis patients and could act as a noninvasive diagnostic tool in this patient group.MethodsThis was a cross-sectional diagnostic test study. 26 dialysis patients with biochemical abnormalities indicating mineral and bone disorder were included. All the participants underwent a 18F-NaF PET scan and a bone biopsy. Fluoride activity in the PET scan was measured in the lumbar spine and at the anterior iliac crest. Dynamic and static histomorphometric parameters of the bone biopsy were assessed. As histomorphometric markers for bone turnover we used bone formation rate per bone surface (BFR/BS) and activation frequency per year (Ac.f).ResultsThere was a statistically significant correlation between fluoride activity in the 18F-NaF PET scan and histomorphometric parameters such as bone formation rate, activation frequency and osteoclast and osteoblast surfaces and mineralized surfaces. 18F-NaF PET's sensitivity to recognize low turnover in respect to non-low turnover was 76% and specificity 78%. Because of the small number of patients with high turnover, we were unable to demonstrate significant predictive value in this group.ConclusionsA clear correlation between histomorphometric parameters and fluoride activity in the 18F-NaF PET scan was established. 18F-NaF PET may possibly be a noninvasive diagnostic tool in dialysis patients with low turnover bone disease, but further research is needed.</div

Myocardial perfusion reserve of kidney transplant patients is well preserved

Background: Chronic kidney disease (CKD) is associated with endothelial dysfunction and increased cardiovascular mortality. Endothelial dysfunction can be studied measuring myocardial perfusion reserve (MPR). MPR is the ratio of stress and rest myocardial perfusion (MP) and reflects the capacity of vascular bed to increase perfusion and microvascular responsiveness. In this pilot study, our aim was to assess MPR of 19 patients with kidney transplant (CKD stages 2–3) and of ten healthy controls with quantitative [15O]H2O positron emission tomography (PET) method.Results: Basal MP was statistically significantly higher at rest in the kidney transplant patients than in the healthy controls [1.3 (0.4) ml/min/g and 1.0 (0.2) ml/min/g, respectively, p = 0.0015]. After correction of basal MP by cardiac workload [MPcorr = basal MP/individual rate pressure product (RPP) × average RPP of the healthy controls], the difference between the groups disappeared [0.9 (0.2) ml/min/g and 1.0 (0.3) ml/min/g, respectively, p = 0.55)]. There was no difference in stress MP between the kidney transplant patients and the healthy subjects [3.8 (1.0) ml/min/g and 4.0 (0.9) ml/min/g, respectively, p = 0.53]. Although MPR was reduced, MPRcorr (stress MP/basal MPcorr) did not differ between the kidney transplant patients and the healthy controls [4.1 (1.1) and 4.3 (1.6), respectively, p = 0.8].Conclusions: MP during stress is preserved in kidney transplant patients with CKD stage 2–3. The reduced MPR appears to be explained by increased resting MP. This is likely linked with increased cardiac workload due to sympathetic overactivation in kidney transplant patients.</p

Bone Histomorphometry and 18F‑Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. F-18-Sodium Fluoride positron emission tomography (F-18-NaF PET) is a dynamic imaging technique that measures turnover. F-18-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a F-18-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche's historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1-L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, F-18-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD

Progression of Aortic Calcification in Stage 4-5 Chronic Kidney Disease Patients Transitioning to Dialysis and Transplantation

Background and Aims: Abdominal aortic calcification (AAC) is common in chronic kidney disease (CKD) patients and associated with increased mortality. Comparative data on the AAC score progression in CKD patients transitioning from conservative treatment to different modalities of renal replacement therapy (RRT) are lacking and were examined. Methods: 150 study patients underwent lateral lumbar radiograph to study AAC in the beginning of the study before commencing RRT (AAC1) and at 3 years of follow-up (AAC2). We examined the associations between repeated laboratory tests taken every 3 months, echocardiographic and clinical variables and AAC increment per year (ΔAAC), and the association between ΔAAC and outcomes during follow-up. Results: At the time of AAC2 measurement, 39 patients were on hemodialysis, 39 on peritoneal dialysis, 39 had a transplant, and 33 were on conservative treatment. Median AAC1 was 4.8 (0.5-9.0) and median AAC2 8.0 (1.5-12.0) (p p = 0.19). ΔAAC was independently associated with mean left ventricular mass index (LVMI) (log LVMI: β = 0.97, p = 0.02) and mean phosphorus through follow-up (log phosphorus: β = 1.19, p = 0.02) in the multivariable model. Time to transplantation was associated with Delta AAC in transplant recipients (per month on the waiting list: β = 0.04, p = 0.001). Delta AAC was associated with mortality (HR 1.427, 95% confidence interval 1.044-1.950, p = 0.03). Conclusion: AAC progresses rapidly in patients with CKD, and ΔAAC is similar across the CKD treatment groups including transplant recipients. The increment rate is associated with mortality and in transplant recipients with the time on the transplant waiting list.</p

Maximal Exercise Capacity in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Renal Replacement Therapy or Continuing Conservative Care: A Longitudinal Follow-Up Study

Introduction: Chronic kidney disease (CKD) is associated with impaired maximal exercise capacity (MEC). However, data are scarce on the development of MEC in CKD stage 4-5 patients transitioning to renal replacement therapy (RRT).Methods: We explored the change in MEC measured in watts (Wlast4) with 2 consecutive maximal bicycle stress ergometry tests in 122 CKD stage 4-5 patients transitioning to dialysis and transplantation in an observational follow-up study.Results: Mean age was 58.9 ± 13.9 years and 43 (35.2%) were female. Mean time between the baseline and follow-up ergometry tests was 1,012 ± 327 days and 29 (23.8%) patients had not initiated RRT, 50 (41.0%) were undergoing dialysis, and 43 (35.2%) had received a kidney transplant at the time of the follow-up ergometry test. The mean Wlast4 was 91 ± 37 W and 84 ± 37 W for the baseline and follow-up ergometry tests, respectively (p Conclusion: MEC declined or remained poor in advanced CKD patients transitioning to RRT or continuing conservative care in this observational study. Mean capillary blood bicarbonate was independently associated with the development of MEC.</p

Association of maximal stress ergometry performance with troponin T and abdominal aortic calcification score in advanced chronic kidney disease

Background: Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied.Methods: One hundred seventy-four CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments.Results: The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e' and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (beta = - 0.09, p = 0.02), AAC (beta = - 1.67, p Conclusions: TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD.</p