Search

Background: Non–vitamin K oral anticoagulants have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of non–vitamin K oral anticoagulants in patients on hemodialysis is not well known. Methods: From June 2017 through May 2022, AXADIA–AFNET 8 (Compare Apixaban and Vitamin K Antagonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease), an investigator-initiated PROBE (prospective randomized open blinded end point) outcome assessment trial, randomized patients with AF on chronic hemodialysis to either apixaban (2.5 mg BID) or the vitamin K antagonist (VKA) phenprocoumon (international normalized ratio, 2.0 to 3.0). The composite primary safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. The primary efficacy outcome was a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis or pulmonary embolism. Our hypothesis was that apixaban is noninferior to VKA. Results: Thirty-nine sites randomized 97 patients (30% women; mean age 75 years; mean CHA 2 DS 2 -VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female sex] score, 4.5; baseline characteristics balanced between groups): 48 to apixaban and 49 to VKA. The median follow-up time was 429 days (range, 37 to 1370) versus 506 days (range, 101 to 1379), respectively. Adherence to apixaban was >80% in 44 of 48 patients; the median time in therapeutic range on VKA was 50.7%. Composite primary safety outcome events occurred in 22 patients (45.8%) on apixaban and in 25 patients (51.0%) on VKA (hazard ratio, 0.93 [95% CI, 0.53–1.65]; P noninferiority =0.157). Composite primary efficacy outcome events occurred in 10 patients (20.8%) on apixaban and in 15 patients (30.6%) on VKA ( P =0.51; log rank). There were no significant differences regarding individual outcomes (all-cause mortality, 18.8% versus 24.5%; major bleeding, 10.4% versus 12.2%; and myocardial infarction, 4.2% versus 6.1%, respectively). Conclusions: In this randomized trial comparing apixaban and VKA in patients with AF on hemodialysis with long follow-up, no differences were observed in safety or efficacy outcomes. Even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Larger randomized trials are needed to determine the optimal anticoagulation regimen for patients with AF on hemodialysis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02933697.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important prophylactic measure in kidney transplant recipients (KTRs), but the immune response is often impaired. Here, we examined the T-cell immune response against SARS-CoV-2 in 148 KTRs after 3 or 4 vaccine doses, including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs than in immunocompetent controls and was correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with messenger RNA and a vector vaccine, and longer time after transplantation. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs.

Zusammenfassung Anamnese Wir berichten über einen 57-jährigen Patienten, der in unserer Klinik zur geplanten AB0-inkompatiblen Lebendnierentransplantation aufgenommen wurde. Untersuchungen und Diagnose An Tag 3 post operationem bildeten sich laborchemisch eindeutige Hinweise für eine Denovo-TMA aus. Die renale Entgiftung stagnierte bei initialem regelrechtem Verlauf. Therapie und Verlauf Durch den Einsatz von Eculizumab 900 mg an d3 und d10 post operationem konnten wir die TMA mit einem anhaltenden Erfolg unterbinden. Folgerung Zu diskutieren ist, ob ein frühzeitiger Einsatz von Eculizumab bei V. a. De-novo-TMA ein sicherer Weg ist, eine Transplantatdysfunktion zu unterbinden und somit die in der Literatur beschriebene schlechte Prognose für Transplantat und Empfänger zu verbessern.

Abstract Chronic hyperglycemia, as in diabetes mellitus, may cause glomerular damage with microalbuminuria as an early sign. Noteworthy, even acute hyperglycemia can increase glomerular permeability before structural damage of the glomerular filter can be detected. Despite intensive research, specific antiproteinuric therapy is not available so far. Thus, a deeper understanding of the molecular mechanisms of albuminuria is desirable. P38 MAPK signaling is involved in the development of hyperglycemia-induced albuminuria. However, the mechanism of increased p38 MAPK activity leading to increased permeability and albuminuria remained unclear. Recently, we demonstrated that acute hyperglycemia triggers endocytosis of nephrin, the key molecule of the slit diaphragm, and induces albuminuria. Here, we identify p38 MAPK as a pivotal regulator of hyperglycemia-induced nephrin endocytosis. Activated p38 MAPK phosphorylates the nephrin c-terminus at serine 1146, facilitating the interaction of PKCα with nephrin. PKCα phosphorylates nephrin at threonine residues 1120 and 1125, mediating the binding of β-arrestin2 to nephrin. β-arrestin2 triggers endocytosis of nephrin by coupling it to the endocytic machinery, leading to increased glomerular permeability. Pharmacological inhibition of p38 MAPK preserves nephrin surface expression and significantly attenuates albuminuria. Key messages Acute hyperglycemia triggers endocytosis of nephrin. Activated p38 MAPK phosphorylates the nephrin c-terminus at serine 1146, facilitating the interaction of PKCα with nephrin. PKCα phosphorylates nephrin at threonine residues 1120 and 1125, mediating the binding of β-arrestin2 to nephrin. β-arrestin2 triggers endocytosis of nephrin by coupling it to the endocytic machinery, leading to a leaky glomerular filter. Pharmacological inhibition of p38 MAPK preserves nephrin surface expression and significantly attenuates albuminuria under hyperglycemic conditions.

Introduction: Pseudohypoaldosteronism type II (PHA II) is a Mendelian disorder, featuring hyperkalemic acidosis and low plasma renin levels, typically associated with hypertension. Mutations in WNK1, WNK4, CUL3, and KLHL3 cause PHA II, with dominant mutations in WNK1, WNK4, and CUL3 and either dominant or recessive mutations in KLHL3. Fourteen families with recessive KLHL3 mutations have been reported, with diagnosis at the age of 3 months to 56 years, typically in individuals with normal kidney function. Methods: We performed clinical and genetic investigations in a patient with hyperkalemic hypertension and used molecular dynamics simulations, heterologous expression in COS7 cells, and Western blotting to investigate the effect of a KLHL3 candidate disease mutation on WNK4 protein expression. Results: The patient, a 58-year-old woman from a consanguineous family, showed hypertension, persistent hyperkalemic acidosis associated with severe muscle pain, nephrolithiasis, chronic kidney disease (CKD), and coronary heart disease. Therapy with hydrochlorothiazide corrected hyperkalemia, hypertension, and muscle pain. Genetic analysis revealed a homozygous p.Arg431Trp mutation at a highly conserved KLHL3 position. Simulations suggested reduced stability of the mutant protein, which was confirmed by Western blot. Compared with wild-type KLHL3, cotransfection of p.Arg431Trp KLHL3 led to increased WNK4 protein levels, inferred to cause increased NaCl reabsorption via the thiazide-sensitive carrier and PHA II. Conclusions: Even in patients presenting late in life and in the presence of CKD, PHA II should be suspected if renin levels are low and hyperkalemic acidosis and hypertension are inadequate for CKD stage, particularly in the presence of a suspicious family history.

BACKGROUND: Patients with kidney failure on dialysis or after renal transplantation have a high risk for severe COVID-19 infection, and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in patients with kidney failure, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in patients on dialysis and in kidney transplant recipients (KTRs) are still needed. METHODS: In this prospective, multicentric cohort study, antibody responses to COVID-19 mRNA vaccines (BNT162b2 [BioNTech/Pfizer] or mRNA-1273 [Moderna]) were measured in 32 patients on dialysis and in 28 KTRs. SARS-CoV-2–specific antibodies and neutralization capacity were evaluated and compared with controls (n=78) of a similar age range. RESULTS: After the first vaccination, SARS-CoV-2–specific antibodies were nearly undetectable in patients with kidney failure. After the second vaccination, 93% of the controls and 88% of patients on dialysis but only 37% of KTRs developed SARS-CoV-2–specific IgG above cutoff. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared with patients on dialysis (503±481 BAU/ml; P

Die arterielle Hypertonie gehort in den westlichen Industrienationen durch ihre hohe Pravalenz zu den haufigsten chronischen Erkrankungen und ist ein Hauptrisikofaktor fur kardiovaskulare Morbiditat und Mortalitat. In der Pathophysiologie der unkontrollierten Hypertonie kommt der Uberaktivitat des sympathischen Nervensystems eine wichtige Bedeutung zu. Seit einigen Jahren steht mit der renalen Denervation (RDN) ein katheterbasiertes Verfahren zur selektiven renalen Sympathektomie zur Verfugung. In mehreren randomisierten, durch Scheinprozedur kontrollierten Studien konnte die Wirksamkeit und Sicherheit des Verfahrens bestatigt werden, sodass davon auszugehen ist, dass die RDN auch klinisch zum Einsatz kommen wird. Ziel der Zertifizierung der Renalen-Denervations-Zentren ist es, einen national verbindlichen Mindeststandard fur Zentren zur Durchfuhrung der RDN zu definieren sowie uber eine Netzwerkbildung die Betreuung der Patienten mit unkontrollierter Hypertonie zu optimieren. Institutionen, welche die RDN durchfuhren, wird im Zuge eines Evaluationsverfahrens die Moglichkeit gegeben, entsprechend zertifiziert zu werden.

Increased sodium intake aggravates cardiovascular diseases. Salt substitute containing potassium chlorideimproves cardiovascular outcome in hypertensive patients with high cardiovascular risk, however it isunknown whether it is attributed to potassium (K+) supplementation or sodium reduction. Here, weinvestigate the role of high K+ intake on the development of hypertensive cardiac damage in the presenceor absence of high salt diet. 8-10 weeks old apolipoproteinE-deficient mice (apoE-KO) were fed a normalK+ (0,55%) or high K+ (5%) diet throughout the experiment. Two weeks after diet start,mice were infusedwith angiotensin (Ang)II (500ng/kg/min) for 28 days. Cardiac function was assessed by MRI. High K+ dietincreased serum K+ levels compared to mice fed a normal K+ diet (5.3±1.2 vs. 3.9±0.4mmol/L, p

Animal studies suggest that adaptive immunity, in particular T cells contribute to the development hypertension. Due to the complex pathophysiological interactions in vivo, the impact of human T cells in the development of hypertension and hypertensive kidney damage is still unknown. To investigate the impact of human T cells, we transferred T cells from treatment resistant hypertensive patients (TRH) and healthy controls (controls) into immunodeficient NOD.Cg-Prkdcscid H2-K1tm1Bpe H2-D1tm1Bpe Il2rgtm1Wjl/SzJ (NSG-(KbDb)null) mice to establish a humanized mouse model. Hypertension was induced by angiotensin (Ang)II (500ng/kg/min) infusion for 14 days. PBMCs from RHT or controls were transferred to NSG-(KbDb) null mice. After ensuring T cell engraftment, blood pressure (BP) was measured by radiotelemetry. At baseline, systolic BP did not differ, however, systolic BP in response to AngII was increased in NSG-(KbDb) null mice receiving PBMCs from TRH compared to controls (week 1: 133±6 vs. 162±3mmHg, p

Vaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs.

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.

Zusammenfassung Anamnese Wir berichten über einen 57-jährigen Patienten, der in unserer Klinik zur geplanten AB0-inkompatiblen Lebendnierentransplantation aufgenommen wurde. Untersuchungen und Diagnose An Tag 3 post operationem bildeten sich laborchemisch eindeutige Hinweise für eine De-novo-TMA aus. Die renale Entgiftung stagnierte bei initialem regelrechtem Verlauf. Therapie und Verlauf Durch den Einsatz von Eculizumab 900 mg an d3 und d10 post operationem konnten wir die TMA mit einem anhaltenden Erfolg unterbinden. Folgerung Zu diskutieren ist, ob ein frühzeitiger Einsatz von Eculizumab bei V. a. De-novo-TMA ein sicherer Weg ist, eine Transplantatdysfunktion zu unterbinden und somit die in der Literatur beschriebene schlechte Prognose für Transplantat und Empfänger zu verbessern.

To assess the performance of two point (2-pt) Dixon-based chemical exchange saturation transfer (CEST) imaging for fat suppression in renal transplant patients.The 2-pt Dixon-based CEST MRI was validated in an egg-phantom and in fourteen renal transplant recipients (5 females and 9 males; age range: 23-78 years; mean age: 51 ± 16.8). All CEST experiments were performed on a 3 T clinical MRI scanner using a dual-echo CEST sequence. The 2-pt Dixon technique was applied to generate water-only CEST images at different frequency offsets, which were further used to calculate the z-spectra. The magnetization transfer ratio asymmetry (MTRResults of the in vitro experiments suggest that the 2-pt Dixon technique enables effective fat peak removal and does not introduce additional asymmetries to the z-spectrum. Accordingly, our results in vivo show that the fat-corrected amide proton transfer (APT) effect in the kidney is significantly higher compared to that obtained from the CEST data acquired close to the in-phase condition both in the renal cortex (-0.1 [0.7] vs. -0.7 [1.2], P = 0.029) and medulla (0.3 [0.8] vs. 0.01 [1.3], P = 0.049), indicating that the 2-pt Dixon-based CEST method increases the specificity of the APT contrast by correcting the fat-induced artifacts.Combination of the dual-echo CEST acquisition with Dixon post-processing provides effective water-fat separation, allowing more accurate quantification of the APT CEST effect in the transplanted kidney.

Aims We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients subtyped by AVS in major referral centres. Methods and results The Adrenal Vein Sampling International Study-2 (AVIS-2) was a multicentre international study that recruited consecutive PA patients submitted to AVS, according to current guidelines, during 15 years. The patients were over 18 years old with arterial hypertension and had an unambiguous diagnosis of PA. The rate of resistant hypertension was assessed at baseline and after adrenalectomy using the American Heart Association (AHA) 2018 definition. Information on presence or absence of resistant hypertension was available in 89% of the 1625 enrolled PA patients. Based on the AHA 2018 criteria, resistant hypertension was found in 20% of patients, of which about two-thirds (14%) were men and one-third (6%) women (χ2 = 17.1, P Conclusions (i) Resistant hypertension is a common presentation in patients seeking surgical cure of PA; (ii) AVS is key for the optimal management of patients with PA due to resistant hypertension; and (iii) AVS-guided adrenalectomy allowed resolution of treatment-resistant hypertension.

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01234220.

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78-519] BAU/ml versus 1826 [560-3180] BAU/ml for KTRs and controls, p

Summary Background Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. Methods In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18–75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02649426 . Findings Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (−8·0 mm Hg [IQR –16·4 to 0·0] vs –3·0 mm Hg [–10·3 to 1·8]; median between-group difference –4·5 mm Hg [95% CI –8·5 to –0·3]; adjusted p=0·022); the median between-group difference was –5·8 mm Hg (95% CI –9·7 to –1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. Interpretation Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. Funding ReCor Medical.

In kidney transplantation, the use of minimally invasive damage biomarkers that are more sensitive and specific than plasma creatinine will be crucial to enable early, actionable detection or exclusion of structural kidney damage due to acute or chronic rejection. Donor-derived cell-free DNA (dd-cfDNA), which can be quantified, for example, through next-generation sequencing, droplet digital PCR and quantitative PCR, is a candidate biomarker with great potential for enabling comprehensive monitoring of allograft injury. dd-cfDNA has a favourable overall diagnostic performance for the detection of rejection and its high negative predictive value might be especially useful for avoiding unnecessary biopsies. Elevated dd-cfDNA levels have been shown to be detectable before graft injury can be clinically identified using current diagnostic methods. Moreover, dd-cfDNA falls rapidly to baseline levels after successful treatment for rejection owing to its short half-life. dd-cfDNA can detect graft injury caused by immune activation owing to insufficient immunosuppression and might therefore also help guide immunosuppression dosing. The fractional abundance of dd-cfDNA can be affected by changes in the recipient cfDNA (for example, due to infection or physical exercise) but the use of absolute quantification of dd-cfDNA overcomes this limitation. Serial dd-cfDNA determinations might therefore facilitate cost-effective personalized clinical management of kidney transplant recipients to reduce premature graft loss.

We report a 57-year-old patient admitted to our hospital for planned AB0-incompatible living kidney transplantation.On day 3 post operationem, clear laboratory evidence of de novo TMA developed. Renal detoxification stagnated with initial regular course.By using eculizumab 900 mg on d3 and d10 post operationem, we were able to suppress TMA with a sustained success.It has to be discussed whether an early use of eculizumab in cases of suspected de novo TMA is a safe way to prevent graft dysfunction and thus to improve the poor prognosis for graft and recipient described in the literature.Wir berichten über einen 57-jährigen Patienten, der in unserer Klinik zur geplanten AB0-inkompatiblen Lebendnierentransplantation aufgenommen wurde.An Tag 3 post operationem bildeten sich laborchemisch eindeutige Hinweise für eine De-novo-TMA aus. Die renale Entgiftung stagnierte bei initialem regelrechtem Verlauf.Durch den Einsatz von Eculizumab 900 mg an d3 und d10 post operationem konnten wir die TMA mit einem anhaltenden Erfolg unterbinden.Zu diskutieren ist, ob ein frühzeitiger Einsatz von Eculizumab bei V. a. De-novo-TMA ein sicherer Weg ist, eine Transplantatdysfunktion zu unterbinden und somit die in der Literatur beschriebene schlechte Prognose für Transplantat und Empfänger zu verbessern.

Zusammenfassung Anamnese Eine 28-jährige Patientin bringt eine Tochter durch primäre Sectio caesarea (41. SSW) bei Beckenendlage zur Welt. Die Schwangerschaft war bis auf erhöhte Blutdruckwerte am Morgen der Sectio komplikationslos. Bei der Sectio kommt es zu einer massiven Blutung aus dem atonen Uterus mit hämorrhagischem Schock. Es erfolgte die Blutstillung durch mechanische Tamponade, die Gabe von Erythrozytenkonzentraten und die Substitution von Gerinnungsfaktoren, auch Tranexamsäure. Bei anurischem Nierenversagen im Rahmen des Schocks wird die Hämodialyse eingeleitet. Untersuchungen/Befunde Klinisch und laborchemisch zeigt sich das Bild einer thrombotischen Mikroangiopathie (TMA). Hinweise auf eine thrombotisch-thrombozytopenische Purpura (TTP) oder ein hämolytisch urämisches Syndrom (HUS) ergeben sich jedoch nicht. Auch ergibt sich bei der genetischen Testung kein Anhalt auf ein atypisches HUS. In der bei persistierender Dialysepflicht nach 4 Wochen durchgeführten Nierenbiopsie kann ein nur teilweise reversibler Tubulusschaden mit älteren ischämischen Rindennekrosen nachgewiesen werden. Therapie und Verlauf Im weiteren Verlauf kommt es zur Wiederaufnahme der Diurese. Bei nicht ausreichender exkretorischer Nierenfunktion muss jedoch die Hämodialyse fortgeführt werden. Glücklicherweise kann bereits ein Jahr nach dem Ereignis bei der Patientin eine Lebendnierentransplantation (Mutter) realisiert werden. Folgerung Die Kombination aus peripartaler Blutung mit hämorrhagischem Schock, möglicherweise aggraviert durch eine peripartale (Prä-)Eklampsie oder ein HELLP-Syndrom, und Applikation von Tranexamsäure mit seiner prothrombotischen Wirkung erscheinen verantwortlich für die schwere renale Rindennekrose.

Supplemental Digital Content is available in the text., Background: Arterial hypertension and its organ sequelae show characteristics of T cell–mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. Methods: To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout–deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg–1·d–1 subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg–1·d–1 subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate. Results: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II–infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout–deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell–depleted angiotensin II–infused mice, suggesting the effect is regulatory T cell–dependent. Conclusions: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease.

Social inequalities in health and disease are well studied. Less information is available on inequalities in biomarker levels indicating subclinical stages of disease such as cystatin C, an early diagnostic marker of renal dysfunction and predictor for cardiovascular disease. We evaluated the relationship between cystatin C, socioeconomic position (SEP) and established cardiovascular risk factors in a population-based study. In 4475 men and women aged 45–75 years participating in the baseline examination of the Heinz Nixdorf Recall Study cystatin C was measured from serum samples with a nephelometric assay. SEP was assessed by education and household income. Linear regression models were used to analyse the association between SEP and cystatin C as well as the impact of cardiovascular risk factors (i.e., body mass index, blood pressure, blood glucose, diabetes mellitus, blood lipids, C-reactive protein, smoking) on this association. After adjustment for age and sex cystatin C decreased by 0.019 mg/l (95% confidence interval (CI) − 0.030 to − 0.008) per five years of education. While using a categorical education variable cystatin C presented 0.039 mg/l (95% CI 0.017–0.061) higher in men and women in the lowest educational category (≤ 10 years of education) compared to the highest category (≥ 18 years). Concerning income, cystatin C decreased by 0.014 mg/l (95% CI − 0.021 to − 0.006) per 1000 € after adjustment for age and sex. For men and women in the lowest income quartile cystatin C was 0.024 mg/l (95% CI 0.009–0.038) higher compared to the highest income quartile. After adjusting for established cardiovascular risk factors the observed associations were substantially diminished. Social inequalities seem to play a role in subclinical stages of renal dysfunction, which are also related to development of cardiovascular disease. Adjustment for traditional cardiovascular risk factors showed that these risk factors largely explain the association between SEP and cystatin C.

Context Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy. Objective This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging. Methods This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. Results In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. Conclusion Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.

Primary aldosteronism (PA) is the most common detectable cause of secondary hypertension. The majority of patients have either an adrenal aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH) demanding different therapeutic approaches. Screening tests and imaging cannot reliably distinguish between a unilateral or bilateral PA. This review article gives an overview concerning etiology, diagnostics, and therapeutic options of PA, and reviews the indication, the technique, and relevance of selective adrenal venous sampling (AVS) in the context of the current literature and the authors' experience. AVS can verify or exclude a unilaterally dominated secretion with a high success rate. Patients with PA and a unilateral APA can be treated curatively by adrenalectomy. AVS is an established diagnostic examination for differentiation of unilateral from bilateral adrenal disease in patients with PA.· Selective adrenal venous sampling (AVS) is a safe, reliable, and minimally invasive method to detect a unilateral or bilateral adrenal adrenal gland disease.. · Verification of lateralization by AVS has direct therapeutic relevance for patients with primary aldosteronism (PA).. · AVS can be performed with low radiation exposure, without contrast medium, and with a high success rate when performed by an experienced interventional radiologist..· Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 - 666. Der primäre Hyperaldosteronismus (PHA; Conn-Syndrom) ist der häufigste nachweisbare Grund für einen sekundären arteriellen Hypertonus. Primäre Ursachen hierfür sind das Aldosteron-produzierende Adenom (APA) oder eine bilaterale adrenale Hyperplasie (BAH) mit jeweils unterschiedlicher therapeutischer Konsequenz. Weder Screening- und Funktionstests noch die Schnittbildgebung können eine unilateral dominante Hormonproduktion nachweisen. Neben einer klinischen Übersicht über Ätiologie, Diagnostik und Therapie des PHA werden in diesem Übersichtsartikel die Indikation, die Technik und der Stellenwert der selektiven Nebennierenvenenblutentnahme (NNVBE) ausführlich dargestellt und im Kontext aktueller Literatur diskutiert. Die NNVBE kann mit hoher Erfolgsrate eine unilaterale Dominanz nachweisen oder ausschließen. Patienten mit PHA und unilateralem APA können kurativ durch eine Adrenalektomie behandelt werden. Die NNVBE ist eine etablierte Intervention zur Subtypisierung des PHA in eine unilaterale oder bilaterale Erkrankung der Nebenniere.· Die Nebennierenvenenblutentnahme (NNVBE) ist eine sichere, zuverlässige und minimalinvasive Methode zur Detektion einer unilateralen oder bilateralen Erkrankung der Nebenniere.. · Der Nachweis einer Lateralisierung durch die NNVBE hat eine unmittelbare Relevanz für die kurative Therapie des primären Hyperaldosteronismus (PHA).. · Die NNVBE kann mit hoher Treffer- und Erfolgsrate ohne Kontrastmittelgabe und mit geringer Strahlenexposition in der Hand eines erfahrenen Untersuchers durchgeführt werden..· Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) – Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 – 666.

The kidney is extensively innervated by sympathetic nerves playing an important role in the regulation of blood pressure homeostasis. Sympathetic nerve activity is ultimately controlled by the central nervous system (CNS). Norepinephrine, the main sympathetic neurotransmitter, is released at prejunctional neuroeffector junctions in the kidney and modulates renin release, renal vascular resistance, sodium and water handling, and immune cell response. Under physiological conditions, renal sympathetic nerve activity (RSNA) is modulated by peripheral mechanisms such as the renorenal reflex, a complex interaction between efferent sympathetic nerves, central mechanism, and afferent sensory nerves. RSNA is increased in hypertension and, therefore, critical for the perpetuation of hypertension and the development of hypertensive kidney disease. Renal sympathetic neurotransmission is not only regulated by RSNA but also by prejunctional α2-adrenoceptors. Prejunctional α2-adrenoceptors serve as autoreceptors which, when activated by norepinephrine, inhibit the subsequent release of norepinephrine induced by a sympathetic nerve impulse. Deletion of α2-adrenoceptors aggravates hypertension ultimately by modulating renal pressor response and sodium handling. α2-adrenoceptors are also expressed in the vasculature, renal tubules, and immune cells and exert thereby effects related to vascular tone, sodium excretion, and inflammation. In the present review, we highlight the role of α2-adrenoceptors on renal sympathetic neurotransmission and its impact on hypertension. Moreover, we focus on physiological and pathophysiological functions mediated by non-adrenergic α2-adrenoceptors. In detail, we discuss the effects of sympathetic norepinephrine release and α2-adrenoceptor activation on renal sodium transporters, on renal vascular tone, and on immune cells in the context of hypertension and kidney disease.

Context Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. Objectives To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. Design and settings In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. Results AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as Conclusion Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020)

Background Increased nerve activity causes hypertension and kidney disease. Recent studies suggest that renal denervation reduces BP in patients with hypertension. Renal NE release is regulated by prejunctional α2A-adrenoceptors on sympathetic nerves, and α2A-adrenoceptors act as autoreceptors by binding endogenous NE to inhibit its own release. However, the role of α2A-adrenoceptors in the pathogenesis of hypertensive kidney disease is unknown. Methods We investigated effects of α2A-adrenoceptor-regulated renal NE release on the development of angiotensin II-dependent hypertension and kidney disease. In uninephrectomized wild-type and α2A-adrenoceptor-knockout mice, we induced hypertensive kidney disease by infusing AngII for 28 days. Results Urinary NE excretion and BP did not differ between normotensive α2A-adrenoceptor-knockout mice and wild-type mice at baseline. However, NE excretion increased during AngII treatment, with the knockout mice displaying NE levels that were significantly higher than those of wild-type mice. Accordingly, the α2A-adrenoceptor-knockout mice exhibited a systolic BP increase, which was about 40 mm Hg higher than that found in wild-type mice, and more extensive kidney damage. In isolated kidneys, AngII-enhanced renal nerve stimulation induced NE release and pressor responses to a greater extent in kidneys from α2A-adrenoceptor-knockout mice. Activation of specific sodium transporters accompanied the exaggerated hypertensive BP response in α2A-adrenoceptor-deficient kidneys. These effects depend on renal nerves, as demonstrated by reduced severity of AngII-mediated hypertension and improved kidney function observed in α2A-adrenoceptor-knockout mice after renal denervation. Conclusions Our findings reveal a protective role of prejunctional inhibitory α2A-adrenoceptors in pathophysiologic conditions with an activated renin-angiotensin system, such as hypertensive kidney disease, and support the concept of sympatholytic therapy as a treatment.

Pre-diabetes, a risk factor for post-transplant diabetes mellitus (PTDM), represents an early therapeutic target for prevention of PTDM. We evaluated glucose metabolism post-transplantation and the ability to predict pre-diabetes and PTDM from haemoglobin A1c (HbA1c) levels at 90 days, at 1 year, and at 3 years in long-term post-transplantation follow-up. HbA1c levels were measured in 71 non-diabetic deceased-donor transplant recipients at four time points (during transplantation, 90-days post-transplantation, 1-year post-transplantion, and at the final post-transplantation follow-up visit 2.71 ± 1.26 years after transplantation). The predictive power of HbA1c levels at 90 days post-transplantation was determined by calculating the sensitivity, specificity, false-positive rates, and false-negative rates. A multivariate logistic regression analysis was performed to determine risk factors for pre-diabetes and PTDM at 1-year post-transplantation and at the last follow-up visit (2.71 ± 1.26 years after renal transplantation). HbA1c values ≥ 5.7% were seen in 79% of patients at 90 days post-transplant, in 83% at 1 year, and in 69% of patients on follow-up. HbA1c cut-off levels of

BACKGROUND Scrupulous comparison of the pharmacokinetic and clinical characteristics of generic tacrolimus formulations versus the reference drug (Prograf) is essential. The pharmacokinetics of the Tacrolimus Hexal (TacHexal) formulation is similar to Prograf in stable renal transplant patients, but data in de novo patients are lacking. METHODS De novo kidney transplant patients were randomized to generic tacrolimus (TacHexal) or Prograf in a 6-month open-label study. RESULTS The primary end point, the dose-normalized area under the curve0-12h at month 1 posttransplant, was similar with TacHexal or Prograf; back-transformed geometric means of adjusted log-transformed values (analysis of variance) were 18.99 ng·h·L (TacHexal) and 20.48 ng·h·L (Prograf) (ratio, 1.08; 90% confidence interval, 0.84-1.38; P = 0.605). The dose-normalized peak concentration geometric means at month 1 was also comparable between treatments (ratio, 1.16; 90% confidence interval, 0.88-1.54; P = 0.377). There were no relevant differences in other pharmacokinetic parameters at month 1 or in area under the curve0-4h and trough concentration when measured at months 3 and 6. The adjusted change in mean estimated glomerular filtration rate from baseline to month 6 (Nankivell) was noninferior for TacHexal versus Prograf using observed values (47.7 vs 38.6 mL/min per 1.73 m, P < 0.001) and was superior based on observed values (P = 0.044) but not using last observation-carried forward method. Rates of biopsy-proven acute rejection (5.7% vs 7.9%), adverse events, and serious adverse events were similar with TacHexal or Prograf. CONCLUSION Tacrolimus pharmacokinetics is similar with TacHexal and Prograf early after kidney transplantation. Efficacy and safety in this limited data set were comparable, with at least equivalent graft function under TacHexal.

The aim of this study was to evaluate the effect of ibandronate administration on long-term graft function and graft survival after successful renal transplantation. Seventy-two renal transplant recipients (36 patients each in the treatment and control group) were included and followed over a 15-year period. Data on graft function and death-censored transplant outcome were recorded at 1, 5, 10, and 15 years. Death-censored Kaplan–Meier analysis showed significantly improved graft survival of the treatment group (p = 0.026), whereas Cox regression analysis showed that ibandronate was positively associated with improved transplant survival (p = 0.028, hazard ratio 0.24, 95% confidence interval 0.07–0.86). Although general linear modelling did not indicate that ibandronate had a significant effect on transplant function (calculated using the estimated glomerular filtration rate according to Chronic Kidney Disease Epidemiology Collaboration equation) over the entire 15-year period (p = 0.650), there was a tendency towards improved graft function 1-year post-transplantion (p = 0.056). Ibandronate treatment within the first year of transplantation resulted in a trend towards better graft function within the first few year post-transplant, and was associated with increased transplant survival at long-term follow-up.

Background: Mortality of critically-ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) in an intensive-care setting continues to remain high. There is still uncertainty as to which factors should guide clinical judgement. Methods: A cohort of 155 patients admitted to an intensive-care unit and necessitating RRT due to AKI were retrospectively analyzed. Demographic and clinical parameters at the time of RRT initiation were retrieved. Multi-and univariate analyses were performed to determine the impact of different risk factors on mortality. Results: The most common causes of AKI were sepsis (39.3%) and cardiac events (32%). The majority of patients were treated by continuous (67.3%), the others by intermittent RRT. After 30 days, 51.0% of patients survived. Nonsurvivors were older (73 vs. 69 years), had a higher APACHEE II score (30.1 +/- 5.6 vs. 26.5 +/- 7.1), and were more likely to be vasopressor dependent, mechanically ventilated, or treated by continuous RRT. Multivariate analysis revealed that higher age, higher APACHEE II score, and lower serum creatinine at baseline were independent predictors for mortality, whereas histories of diabetes mellitus, arterial hypertension, coronary heart disease, or stroke were not. Conclusion: Critically-ill patients with AKI requiring RRT continue to have a high mortality. Age and APACHE II score showed an impact on mortality whereas traditional cardiovascular risk factors did not. Higher BUN and creatinine levels do not have a negative impact on mortality. Our findings support the current practice that RRT initiation should primarily be guided by clinical decision.

SummaryDirect oral anticoagulants (DOACs) are increasingly prescribed substances in patients with indication for effective anticoagulation. Patients with chronic kidney disease (CKD) have a high burden of cardiovascular risk and are more likely to develop atrial fibrillation (AF) than patients without CKD. Patients with mild to moderate CKD benefit from DOACs, especially when having intolerance to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients with rare renal disease and hypercoagulabilic state. DOACs are to a large extent eliminated by renal excretion. Since prospective randomised data in CKD patients are sparse, the decision for anticoagulative therapy is challenging especially in patients with severe renal impairment. The direct factor Xa-inhibitors are approved for use even in patients with an estimated glomerular filtration rate (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a regular basis is essential before initiation and after start of DOAC, especially for patients at risk for acute renal failure (elderly, diabetics, patients with preexisting kidney disease). None of the DOACs is approved in CKD patients with end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors. In these patients conventional therapy with VKA is the only option, which has to be monitored closely since it has potential adverse effects.

Chronic high salt (NaCl) intake is a major risk factor for cardiovascular diseases. Recent studies showed that excessive chronic NaCl intake affects immune response and thereby contributes to the pathogenesis of vascular injury. However, it remains unclear whether NaCl intake initially primes immune cell response by promoting memory T cells and sensitize the development of vascular injury in response to a subsequent stimulus. Therefore, we investigate whether 14 days of NaCl treatment (1% NaCl) followed by a 7 day washout period affects the incidence and outcome of abdominal aortic aneurysms (AAA) in apolipoprotein E deficient (ApoE-KO) mice infused chronically with angiotensin II (Ang II) (1000ng/kg/min) via osmotic minipumps for 10 days. Assessment of AAA was done by magnetic resonance imaging (MRI). To visualize vascular inflammation in vivo , perfluorocarbon nano-emulsions (PFC) injected intravenously before and 2, 4, 7 and 10 days after chronic Ang II infusion were detected by combining 1H/19F MRI using a 19 F RARE sequence. After 10 days of Ang II infusion, aortas with perivascular fat were dissected. Aortic inflammation and immune cells infiltration were analyzed by flow cytometery, immunohistology and realtime PCR. The survival rate of ApoE-KO mice pretreated with NaCl was significant lower and the AAA incidence rate was significant higher compared to non-NaCl treated apoE-KO mice. The amount of 19 F signal detected in areas of AAA was significantly increased in apoE-KO mice pretreated with NaCl. Histological analysis confirmed these results. At day 10, proinflammatory cytokines like TNF-alpha, iNOS and TGF-ß as well as numbers of neutrophils, monocytes as well as effector memory CD4 and CD8 T cells were significantly higher in aortas of NaCl pretreated apoE-KO mice compared to non-NaCl treated mice. In conclusion, these results suggest a significant role of NaCl in priming immune cell phenotype and thereby mediating vascular inflammation and damage in Ang II infused apoE-KO mice.

Data on trends of end-stage renal disease among people with diabetes are lacking. We analysed the incidence of end-stage renal disease, defined as renal replacement therapy, among people with and without diabetes, and the corresponding relative risk. Moreover, we investigated time trends for the period 2002–2016. In this retrospective population-based study we analysed data from one dialysis centre of a region in Germany covering a population of about 310,000 inhabitants. We estimated the age- and sex-standardised incidence rates for chronic renal replacement therapy among adults with and without diabetes and the corresponding relative risks. The time trend was analysed using Poisson regression models. Between 2002 and 2016, 1107 people (61.2% male; mean age 71.6 years; 48.7% with diabetes) had a first renal replacement therapy. During the study period, the incidence rate in the population with diabetes varied from 93.6 (95% CI 50.4, 136.7) in 2002 to 140.5 (95% CI 80.6, 200.4) in 2016 per 100,000 person-years. In the population without diabetes the incidence rate was substantially lower and reached 17.3 (95% CI 10.9, 23.6) in 2002 and 24.6 (95% CI 17.5, 31.7) in 2009. The relative risk comparing people with and without diabetes was 3.57 (95% CI 3.09, 4.13). No significant change in the incidence rates was found during the observation period, either in the population with or in the population without diabetes, and thus the relative risk also remained constant. People with diabetes have a higher risk of needing renal replacement therapy than those without diabetes, a fact that remained constant over a time period of 15 years.

The loss of albumin in urine (albuminuria) predicts cardiovascular outcome. Under physiological conditions, small amounts of albumin are filtered by the glomerulus and reabsorbed in the tubular system up until the absorption limit is reached. Early increases in pathological albumin filtration may, thus, be missed by analyzing albuminuria. Therefore, the use of tracers to test glomerular permselectivity appears advantageous. Fluorescently labeled tracer fluorescein isothiocyanate (FITC)-polysucrose (i.e., FITC-Ficoll), can be used to study glomerular permselectivity. FITC-polysucrose molecules are freely filtered by the glomerulus but not reabsorbed in the tubular system. In mice and rats, FITC-polysucrose has been investigated in models of glomerular permeability by using technically complex procedures (i.e., radioactive measurements, high-performance liquid chromatography [HPLC], gel filtration). We have modified and facilitated a FITC-polysucrose tracer-based protocol to test early and small increases in glomerular permeability to FITC-polysucrose 70 (size of albumin) in mice. This method allows repetitive urine analyses with small urine volumes (5 µL). This protocol contains information on how the tracer FITC-polysucrose 70 is applied intravenously and urine is collected via a simple urinary catheter. Urine is analyzed via a fluorescence plate reader and normalized to a urine concentration marker (creatinine), thereby avoiding technically complex procedures.

A 28-years old patient delivers a daughter by primary caesarian section (41. WOP) in breech presentation after a complication-free pregnancy except increased blood pressure readings at the morning of caesarian section. During the caesarian section a major bleeding of the atonic uterus with hemorrhagic shock appears. Haemostasis is achieved by mechanical tamponade, the application of red blood cell concentrates and the substitution of clotting factors, also tranexamic acid. Because of an anuric renal failure due to the shock hemodialysis is initiated.Clinical examination and blood tests show the constellation of a thrombotic microangiopathy. There are no hints for a thrombotic thrombocytopenic purpura (TTP) or a hemolytic-uremic syndrome (HUS). In addition, a genetic testing gives no hints for an atypical HUS. After 4 weeks of dialysis duty a renal biopsy is performed. The renal biopsy shows a partly reversible tubular damage with an older ischemic cortical necrosis.In the further course the resumption of the diuresis can be observed. The dialysis treatment has to be continued because of an insufficient excretory renal function. Fortunately a living-donor kidney transplantation (mother) can be carry out successfully already one year after the hemorrhagic shock.The combination of peripartal bleeding with hemorrhagic shock, possibly aggravated by (pre-)eclampsia or HELLP-syndrome, and the application of tranexamic acid with its prothrombotic effect seems to be responsible for the major renal cortical necrosis.Eine 28-jährige Patientin bringt eine Tochter durch primäre Sectio caesarea (41. SSW) bei Beckenendlage zur Welt. Die Schwangerschaft war bis auf erhöhte Blutdruckwerte am Morgen der Sectio komplikationslos. Bei der Sectio kommt es zu einer massiven Blutung aus dem atonen Uterus mit hämorrhagischem Schock. Es erfolgte die Blutstillung durch mechanische Tamponade, die Gabe von Erythrozytenkonzentraten und die Substitution von Gerinnungsfaktoren, auch Tranexamsäure. Bei anurischem Nierenversagen im Rahmen des Schocks wird die Hämodialyse eingeleitet.Klinisch und laborchemisch zeigt sich das Bild einer thrombotischen Mikroangiopathie (TMA). Hinweise auf eine thrombotisch-thrombozytopenische Purpura (TTP) oder ein hämolytisch urämisches Syndrom (HUS) ergeben sich jedoch nicht. Auch ergibt sich bei der genetischen Testung kein Anhalt auf ein atypisches HUS. In der bei persistierender Dialysepflicht nach 4 Wochen durchgeführten Nierenbiopsie kann ein nur teilweise reversibler Tubulusschaden mit älteren ischämischen Rindennekrosen nachgewiesen werden.Im weiteren Verlauf kommt es zur Wiederaufnahme der Diurese. Bei nicht ausreichender exkretorischer Nierenfunktion muss jedoch die Hämodialyse fortgeführt werden. Glücklicherweise kann bereits ein Jahr nach dem Ereignis bei der Patientin eine Lebendnierentransplantation (Mutter) realisiert werden.Die Kombination aus peripartaler Blutung mit hämorrhagischem Schock, möglicherweise aggraviert durch eine peripartale (Prä-)Eklampsie oder ein HELLP-Syndrom, und Applikation von Tranexamsäure mit seiner prothrombotischen Wirkung erscheinen verantwortlich für die schwere renale Rindennekrose.