Search

Old age was identified as a strong risk factor for acute kidney injury (AKI). Our objectives were to provide estimates of AKI, risk factors and outcomes in patients ≥ 75 years for whom data are scarce.Observational studies and randomized controlled trials between 2005 and 2021 with patients of mean or median age ≥ 75 years, reporting AKI according to current definitions. Data on AKI incidence, risk factors and mortality were analyzed separately in unselected (UC) and acute heart failure (AHF) cohorts.Twenty-six observational studies and 4 randomized controlled trials with 51,111 UC and 25,414 AHF patients were included. Ages averaged 79.4 and 79.8 years, respectively. Pooled risk ratios (RRs) of AKI rates were 26.29% (95% confidence intervals (CI) 13.20-41.97) (UC) and 24.21% (95% CI 20.03-28.65) (AHF). In both cohorts, AKI was associated with decreased estimated glomerular filtration rate at baseline, chronic kidney disease (UC: RR 1.80 (95% CI 1.15-2.80), AHF: RR 1.51 (95% CI 1.26-1.95) and hypertension (UC: RR 1.30 (95% CI 1.09-1.56), AHF: RR 1.07 (95% CI 1.05-1.09). RRs of AKI in patients on renin-angiotensin-inhibitors were 0.87 (95% CI 0.78-0.97) and 0.88 (95% CI 0.78-0.98) in UC and AHF, respectively. AKI was consistently associated with increased risk of in-hospital mortality (UC: RR 3.15 (95% CI 2.28-4.35), AHF: RR 4.28 (95% CI 2.53-7.24).AKI is frequent in patients ≥ 75 years. While reduced renal function at baseline, CKD and hypertension were associated with AKI development, renin-angiotensin-inhibitors may be protective. Older AKI patients showed higher short-term mortality rates.

in press

Most studies on health-related quality of life (HRQoL) in chronic kidney disease (CKD) focus on patients with end-stage kidney disease although they represent a small proportion of patients with CKD. We aimed to analyze HRQoL according to glomerular filtration rate (GFR) categories in a population-based sample of adults living in Germany. Methods: Data from the German health interview and examination survey conducted from 2008 to 2011 were used. Participants with valid interview and examination data aged 40–79 years were included (n = 5,159). Serum creatinine levels were used to calculate estimated GFR via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We classified kidney function in GFR categories according to the Kidney Disease Improving Global Outcomes Initiative (KDIGO) guidelines on CKD: G1 (high): ≥90 mL/min/1.73 m2, G2 (normal): 60–89 mL/min/1.73 m2, G3a (mildly decreased): 45–59 mL/min/1.73 m2, G3b (moderately decreased): 30–44 mL/min/1.73 m2, G4/5 (severely decreased/end-stage kidney disease): 2. HRQoL was evaluated with the Short Form Health Survey (SF-36). Different multivariate linear and logistic regression models were used to analyze the association of HRQoL with GFR categories. Results: Overall, 5.9% had a GFR 2 (corresponding to categories G3a, G3b, and G4/5). Compared to category G2 linear regression showed a decline in physical HRQoL in categories G3a (−2.34, p = 0.004), G3b (−5.37, p = 0.009), and G4/5 (−4.82, p = 0.117). No decline in mental HRQoL was detected with increasing GFR categories. Categories G3a to G4/5 were significantly associated with a low perceived general state of health (G3a: odds ratio [OR] = 2.03, p = 0.001; G3b: OR = 3.01, p = 0.009; G4/5: OR = 8.70, p = 0.016) when compared to category G2. Conclusion: In a representative sample of adults living in Germany, both physical HRQoL and the perceived general state of health are already significantly reduced in category G3a.

Purpose: Severe and fatal Capnocytophaga canimorsus infection has been described in immunocompromised patients. Data of C. canimorsus infection in immunocompetent and risk factors of severe courses...

We assessed agreement, accuracy, precision, and reliability of retrospectively compared with prospectively and separately attained, retrospective Clinical Frailty Scale (CFS) scoring, respectively. Compared to both prospectively and separately retrospectively attained CFS, retrospective CFS scores demonstrated high agreement, accuracy, precision, and reliability in 110 hospitalized patients aged ≥ 80 years. The retrospectively attained CFS score is a valid diagnostic instrument to measure frailty in older hospitalized patients. There is a considerable need to measure frailty retrospectively in clinical practice and research. We assessed agreement, accuracy, precision, and reliability of retrospectively compared with prospectively, and separately attained, retrospective Clinical Frailty Scale (CFS) scoring, respectively. We studied 110 hospitalized patients aged ≥ 80 years, consisting of 70.9% females. Agreement was assessed by bias, accuracy by root mean square error (RMSE) and the percentages of one CFS scores within 20% and 30% of each other (P20 and P30), precision by interquartile ranges of the bias, and reliability by weighted Cohen’s kappa (κ). Comparison of retrospective and prospective CFS scores demonstrated a modest bias of 0.26. Classification as robust, prefrail, or frail was generally correct in retrospectively compared to prospectively CFS scores. RMSE was low (0.28), while P20 and P30 values were high (90.0% and 96.6%, respectively). Precision of retrospective to predict prospective CFS scores was high with narrow interquartile ranges of 0 and 1. Reliability of retrospective with prospective CFS scores was high (κ = 0.89). Comparing two separately attained retrospective CFS scores demonstrated low bias (0.05) and RMSE (0.24), and a high P30 value (90.0%). Precision and interrater reliability of the comparison of retrospective CFS scores were high with narrow interquartile ranges and κ = 0.85. The retrospectively attained CFS score is a valid diagnostic instrument to measure frailty in older hospitalized patients with high agreement, accuracy, precision, and reliability compared to both prospective and separately attained CFS scores.

Aims Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA. Methods Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years. Results Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%. Conclusions NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Objectives Renal insufficiency is common among older patients and, accordingly, renally excreted drugs may require an adjustment in dosage for them. Rates of non-adherence to renal dosing guidelines range from 19% to 70% across all settings, with the highest rate occurring in outpatient care. However, there is a paucity of research in this field. The main objective of this systematic review is to assess how often drugs are inappropriately prescribed in non-hospitalized patients with renal insufficiency. Design A systematic literature search was performed. Data were identified from three electronic databases: PubMed, CINAHL, and Scopus. Studies were included if they reported quantitative data on inappropriate drug use with respect to renal function in non-hospitalized patients. Results Our search strategy resulted in 2,403 hits, of which 18 articles satisfied the criteria for inclusion. Mean estimated glomerular filtration rate ranged from 36.0 to 60.4 mL/min. Prevalence of renally inappropriate drug use ranged from 1% to 37% in outpatient settings other than nursing homes, and from 6% to 43% in nursing homes. Eight of the studies we included identified predictors for use of drugs inappropriate for kidney function. Most frequently determined risk factors were increasing age and a high number of prescribed drugs. Conclusion Lack of dose adjustment for renal impairment seems to be a common problem, even in outpatients. However, the differences in methodologies used in these studies hampered any direct comparison. Accepted and comparable standards regarding the drugs included in the studies as well as estimation of renal function would be beneficial.

Vitamin K antagonists (VKAs) are susceptible to drug–drug interactions. Non-VKA oral anticoagulants (NOACs) have a decreased sensitivity to pharmacokinetic interactions and might be therefore considered superior in patients treated with multiple drugs. The objective of this study was to compare the risk of serious bleeding associated with interacting drugs in German nursing home residents treated with VKA or NOAC. Using claims data of new nursing home residents aged ≥ 65 years (2010–2014) we conducted separate nested case–control analyses within two cohorts of patients treated with VKA or NOAC, respectively. Cases were defined as patients hospitalized for serious bleeding. For each case, up to 20 controls were selected by risk-set sampling. Conditional logistic regression was used to obtain confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the risk of bleeding associated with VKA or NOAC use and interacting drugs compared with the use of the respective oral anticoagulant alone. Among 127,227 new nursing home residents, 16,804 patients received oral anticoagulation. Based on 372 cases and 7281 matched controls, the highest risk of bleeding in VKA users was observed for the concomitant use of antibiotics (aOR 3.00; CI 2.11–4.27) vs. VKA use alone, followed by non-steroidal anti-inflammatory drugs (1.66; 1.13–2.43). Among 243 NOAC cases and 4776 matched controls, elevated risks for bleeding were observed for the use of heparins (2.05; 1.25–3.36) and platelet inhibitors (1.92; 1.36–2.72). Concomitant medication needs to be prescribed cautiously and monitored closely in nursing home residents treated with oral anticoagulants.

Hintergrund In Deutschland leben ungefahr 800.000 Menschen in Pflegeeinrichtungen. Die arztliche Versorgung erfolgt durch ambulant tatige Haus- und Facharzte. Wahrend nahezu alle Bewohner regelmasigen Kontakt zu Hausarzten haben, gilt dies fur andere Facharztgruppen nur in unterschiedlichem Ausmas.

International audience; Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures. Even more challenging is the multifactorial origin of AKI and the fact that the changes of molecular expression induced by AKI are difficult to distinguish from those of the diseases associated or causing AKI as shock or sepsis. During the past decade, a considerable number of protein biomarkers for AKI have been described and we expect from recent advances in the field of omics technologies that this number will increase further in the future and be extended to other sorts of biomolecules, such as RNAs, lipids, and metabolites. However, most of these biomarkers are poorly defined by their AKI-associated molecular context. In this review, we describe the state-of-the-art tissue and biofluid proteomic and metabolomic technologies and new bioinformatics approaches for proteomic and metabolomic pathway and molecular interaction analysis. In the second part of the review, we focus on AKI-associated proteomic and metabolomic biomarkers and briefly outline their pathophysiological context in AKI.

Acute kidney injury (AKI) is a severe complication after infrarenal abdominal aortic aneurysm (iAAA) repair. Little data are available whether endovascular aneurysm (EVAR) or open aortic repair (OAR) differs with respect to AKI frequency and severity, consecutive development of chronic kidney disease (CKD) and potentially preventable and modifiable risk factors of AKI. We assessed AKI rates, AKI stages and CKD applying current, complete definitions from the kidney disease improving global outcomes initiative in propensity-score-matched cohorts of all patients with elective and urgent iAAA repair at our institution from 2007 to 2011. Risk factors were analysed using multivariate logistic regression analyses. From 268 patients, we identified 91 matched pairs who had undergone either EVAR or OAR. The AKI rate was 13.2% with EVAR versus 41.8% with OAR (P

Background Permanent renal function decline, and development and deterioration of chronic kidney disease (CKD) are associated with serious complications. How frequent is renal function decline after infrarenal abdominal aortic aneurysm (iAAA) repair according to current definitions and what are its risk factors, especially potentially modifiable ones? Methods Retrospective observational study including all patients with elective or urgent iAAA repair from 2007 to 2011. The primary outcome was renal function decline in the first year after iAAA repair, defined as permanent reduction of estimated glomerular filtration rate (eGFR) ≥20% from baseline and/or end-stage renal disease (ESRD), all in the first year after iAAA repair. According to current Kidney Disease Improving Global Outcomes guidelines, CKD and periprocedural AKI were defined and classified. Multivariate Cox proportional hazards model was used to assess associations of the primary end point with potential risk factors. Results Two hundred sixty-eight patients with iAAA repair were studied, 61 patients (22.7%) developed declining eGFR ≥20% and/or ESRD. The primary end point was independently associated with preexisting CKD (hazard ratio [HR] 3.14 [1.61–6.09]), renal artery stenosis (RAS) ≥70% (HR 4.34 [1.49–12.67]), open aortic aneurysm repair (OAR) (HR 1.69 [1.14–2.68]), and periprocedural AKI (HR 15.25 [7.49–31.05]). When comparing the subsets of patients with and without OAR and periprocedural AKI, these 2 modifiable risk factors had an additive impact. Declining eGFR ≥20% and/or ESRD was most frequent in patients receiving OAR who developed AKI. Conclusions A permanent decline of renal function 1 year after iAAA repair is frequent. Preexisting CKD, RAS ≥70%, OAR, and periprocedural AKI are independent risk factors, the latter 2 with additive effect.

Background Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis. Methods Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls. Results From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72–0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1). Conclusions This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1344-z) contains supplementary material, which is available to authorized users.

Background Nursing home residents often suffer from a multiplicity of medical conditions and take many different drugs. Many drugs are eliminated via the kidneys and thus require dose adjustment in patients with renal insufficiency. This is the first study to address the prevalence of renal insufficiency among nursing home residents in Germany, and the extent to which such persons take drugs that are contraindicated or incorrectly dosed because of renal insufficiency.

The aims of this study were to compare estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, to assess the classification of chronic kidney disease (CKD) stages by both equations, and to identify factors associated with differences between both equations in patients with or at high risk of CKD managed in primary care.This was an observational study of 803 patients with CKD, long-standing, severe hypertension and diabetes exclusively managed in primary care. Bias and precision between the two equations used to calculate eGFR were quantified as proposed by Bland and Altman.In 1534 eGFR calculations, mean eGFR(MDRD) was 0.8 ± 3.6 ml/min/1.73 m(2) higher than eGFR(CKD-EPI). Precision between the two equations was ±7.1 ml/min/1.73 m(2). Classification of CKD stages by MDRD or CKD-EPI equations agreed in 93.3% of cases. Age above 70 years, eGFR below 60 and above 120 ml/min/1.73 m(2) were associated with higher eGFR(MDRD) values; and age below 50 years and inadequately controlled hypertension with higher eGFR(CKD-EPI) values.Comparison of eGFR calculated by MDRD and CKD-EPI equations demonstrated no clinically relevant difference. In addition, CKD classification by both equations agreed highly. As both equations performed equally well, the simpler and more established MDRD equation should be preferred in patients with or at high risk of CKD managed in primary care. Patients' characteristics seem to account for previously reported differences in the performance of CKD-EPI and MDRD equations.

Das akute Nierenversagen (ANV) tritt, nach der aktuell entwickelten Definition, mit einer Inzidenz von bis zu 30% nach kardiochirurgischen Eingriffen auf, bei etwa 1% der Betroffenen als dialysepflichtiges Nierenversagen, weshalb der Begriff „cardiac surgery associated acute kidney injury“ (CSA AKI) gepragt wurde. Die ANV-assoziierte Mortalitat liegt zwischen 15 und 30% und CSA AKI erhoht die Mortalitat, unabhangig von der Komorbiditat. Lediglich bei 50% der Uberlebenden kommt es zur vollkommenen Regeneration der Nierenfunktion. Die Pathophysiologie des CSA AKI ist keineswegs auf den Einsatz der extrakorporalen Zirkulation begrenzt, sondern ausgesprochen komplex und multifaktoriell und beinhaltet v. a. endogene und exogene Nephrotoxine, Inflammation, Hypoperfusion sowie metabolische und neurohormonale Faktoren. Es existiert keine kausale Therapie des CSA AKI; extrakorporale Nierenersatzverfahren stellen lediglich eine supportive Therapie des ANV dar, um die Zeit bis zur renalen Regeneration zu uberbrucken. Daher kommt der primaren und sekundaren Pravention des ANV mit Korrektur aller vermeidbaren und modifizierbaren Risikofaktoren die entscheidende Rolle zu.

Multiple myeloma (MM) is frequently complicated by renal insufficiency, which is associated with an unfavorable prognosis. Serum cystatin C is a new and accurate marker of glomerular filtration rate. Global gene expression analysis has revealed serum cystatin C as one of the most highly upregulated genes in MM. Recent data have shown serum cystatin C as an independent prognostic marker in MM. To further elucidate the prognostic significance of serum cystatin C, we investigated pretreatment serum cystatin C levels in 68 newly diagnosed patients homogeneously treated with high-dose melphalan followed by autologous stem cell transplantation. Median serum cystatin C level in MM patients was significantly higher than in the 66 healthy controls (1.07 vs. 0.74 mg/L [p = 0.002]). Median serum cystatin C levels significantly increased with higher International Staging System (ISS) stages (stage I 0.72 mg/L; stage II 0.89 mg/L; stage III 1.28 mg/L; p < 0.0001). Higher serum cystatin C was positively correlated with higher serum levels of creatinine (r = 0.84; p < 0.0001), β2-microglobulin (r = 0.72; p < 0.0001), LDH (r = 0.43; p = 0.0003), white blood cell counts (r = 0.61; p < 0.0001) and calcium (r = 0.29; p = 0.016), and negatively correlated with lower serum albumin levels (r = 0.44; p < 0.0001) and hemoglobin levels (r = 0.31; p = 0.01). Using ROC analysis, patients with serum cystatin C levels ≥0.95 mg/L (n = 24) had a significantly shorter event-free survival (EFS) and overall survival (OS) than patients with serum cystatin C levels

Background: It is critical to preserve residual renal function (RRF) in peritoneal dialysis (PD), as RRF is associated with lower morbidity and mortality. There is no uniform definition of RRF, and rapidly declining RRF has rarely been studied and predominately limited to single factor analysis and not corrected for lead-time bias. Methods: An observational study in 71 incident PD patients. RRF was defined as urine output (UO) ≥500 ml/day and renal glomerular filtration rate (rGFR) ≥2 ml/min/1.73 m2, rapid declining RRF as UO 2 occurring within 6 months which were separately evaluated. Independent risk factors associated with rapid RRF decline were identified while correcting for lead-time bias. Results: RRF declined rapidly by both definitions in 65% patients 2.5 years after PD start. Both definitions of RRF decline were consistent in 96%. Nephrotoxic drugs, renal transplant failure and absent angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) were independent risk factors associated with rapidly declining RRF defined both by definitions, intravascular radiocontrast additionally for UO decline. Conclusions: Most PD patients demonstrated rapid RRF decline, independent of its definition. Both definitions are highly consistent and interchangeable. Nephrotoxic drugs and radiocontrast were identified as risk factors of acute, absent ACEI or ARB, and renal transplant failure of chronic renal injury.

Polypharmacy has become an emerging public health issue in recent years, since use of multiple medications or polypharmacy is beneficial for many conditions, but may also have negative effects like adverse drug reactions. The risk further increases in patients with chronic renal failure, a comorbidity very frequent in nursing home residents. Since more than 50 % of all drugs were renally excreted, dose adjustments in patients with renal failure are required. To assess polypharmacy in German nursing homes, in particular in residents with renal failure. Multi-center cross-sectional study in 21 nursing homes in Bremen and Lower Saxony/Germany. Baseline data were analysed using descriptive statistics. Multivariable logistic regression model and 95 % confidence intervals were used to study the association of renal failure and polypharmacy. Of all 852 residents, the analysis comprised those 685 with at least one serum creatinine value so that the estimated creatinine clearance could be calculated. Of those, 436 (63.6 %) had a severe or moderate renal failure, defined as estimated creatinine clearance

The euroSCORE is a widely applied scoring system to estimate perioperative risk in patients undergoing cardiac surgery. It acknowledges an increased risk in women but does not apply a gender-specific weighing of individual risk indicators. We separately investigated the performance of the euroSCORE for men and women. Cardiac surgical patients operated in 2002 and 2003 (n = 1930) served as training group. Patients operated in 2004 served as validation group (n = 870). Using binary regression analysis, we developed a gender-specific model on the basis of the original euroSCORE risk indicators. The individual risk indicators were assigned gender-specific correlation coefficients. Applying ROC analysis to the validation group, the original euroSCORE performed well, with an area under curve (AUC) of 0.758, for men but poor, with an AUC 0.676, for women. After gender-specific re-weighing, ROC analysis revealed considerably improved predictive values of the modified euroSCORE. AUC for women increased to 0.755, AUC for men further increased to 0.772. The original euroSCORE failed to accurately predict perioperative mortality in women. A binary regression model, assigning a gender-specific weight to each of the risk indicators of the original euroSCORE, considerably improved the predictive power of the modified euroSCORE.

Early and accurate detection of acute kidney injury (AKI) is needed to prevent the progression to chronic kidney disease and to improve outcome. Here we used capillary electrophoresis-mass spectrometry to identify urinary peptides predictive of AKI in a training set of 87 urine samples longitudinally collected from patients in an intensive care unit. Within this patient cohort, 16 developed AKI while 14 maintained normal renal function. The sequence of twenty peptides significantly associated with AKI was identified. They were found to be degradation products of six proteins. These formed a diagnostic pattern. Peptides of albumin, α-1-antitrypsin, and β-2-microglobulin were upregulated but fragments of fibrinogen α and collagens 1 α(I) and 1 α(III) were downregulated in AKI. After cross-validation of the training set, a good diagnostic performance of the marker pattern was found with an area under the ROC curve of 0.91. This was confirmed in a blinded validation set of 20 patients in the intensive care unit and 31 allogeneic hematopoietic stem cell transplantation patients, of which 13 had and 18 had not experienced an episode of AKI. In comparison to more established markers of AKI such as serum cystatin C and urinary kidney injury molecule-1, interleukin-18, and neutrophil gelatinase associated-lipocalin, the proteomic marker pattern was found to be of superior prognostic value, detecting AKI up to 5 days in advance of the rise in serum creatinine.

Summary Aims: To assess the impact of late referral (LR) for nephrological co-management compared with early referral (ER) on morbidity and mortality in chronic kidney disease (CKD) and to identify individual factors associated with higher mortality in LR, correcting for lead-time and immortal time bias. Patients and methods: Retrospective observational study comparing 46 LR patients with 103 ER patients. The quality of CKD management was assessed by measures to prevent CKD progression and to modify CKD complications and cardiovascular risk factors according to current guidelines. One-year mortality of LR and ER was compared and factors associated with mortality were identified. Analysis was performed with equivalent GFR (glomerular filtration rate) of ER and LR at baseline to correct for lead-time and immortal time bias. Results: Late referral was associated with inferior control of most risk factors for CKD progression, CKD complications and cardiovascular risk factors. In particular, glycaemic control, the use of angiotensin converting enzyme inhibitors and angiotensin-2-receptor blockers in diabetic nephropathy or proteinuria, the control of nutritional and volume status were inferior in LR. One-year mortality was significantly higher in LR (RR 5.9 (95% CI 1.5–19.6); p

Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides.

Acute kidney injury (AKI) is the most common acute renal condition. AKI is associated with an increase of morbidity and mortality independently of other conditions. Only during the last years, a uniform definition of AKI has been developed which also incorporates small increments of serum creatinine. As no effective therapy of AKI is available, the focus is on prevention of AKI. In most patients, several risk factors or causes of AKI are present. The rapid identification of all avoidable and modifiable risk factors and subsequently the rapid and complete modification are essential. Only these measures seem to decrease morbidity and mortality associated with AKI.

In addition to extracorporeal renal replacement strategies, which in chronic kidney disease (CKD) are largely reserved for the treatment of end-stage kidney failure, conservative measures can be taken to reduce concentration, effects, or both concentration and effects of uremic retention solutes. In this overview, we will focus on those therapies, which are aimed at preventing or delaying cardio-vascular disease, retarding or halting the progression of CKD, or both. We will discuss, consecutively, inhibitors of the renin-angiotensin-aldosterone axis, beta-blockers, calcium-channel antagonists, anti-inflammatory drugs, intestinal sorbents, calcimimetics, and glitazones. Some of these approaches could lead to a therapeutic breakthrough in the future. In addition, comprehensive tables will be provided for more traditional therapeutic approaches, such as lifestyle changes and other pharmaceutical treatments.

Acute kidney injury (AKI) is a serious and frequent complication after coronary artery bypass grafting (CABG). Cardiopulmonary bypass (CPB) was identified as a major AKI risk factor after CABG. Our aim was to assess the impact of the off-pump coronary artery bypass (OPCAB) compared to the on-pump coronary artery bypass (ONCAB) technique on the rate and severity of AKI, while taking other risk factors for AKI into account.An observational study of 201 consecutive adult patients was conducted; 100 were operated by the OPCAB and 101 by the ONCAB technique. All patients in each group were operated by a single, experienced surgeon. Fifteen pre-, intra- and postoperative variables that were repeatedly identified in previous studies as independent AKI risk factors were included in this analysis. AKI was defined as an increase of serum creatinine/=50% or/=0.3 mg/dL within 48 h and AKI severity was classified, according to current AKIN definitions.Significantly fewer OPCAB patients developed AKI compared to ONCAB (14.0 versus 27.7%; P = 0.03). OPCAB was associated with milder stages of AKI, whereas ONCAB patients had more severe AKI. Congestive heart failure and chronic kidney disease were independent risk factors for AKI. The OPCAB technique for CABG was identified as the only independent factor associated with lower incidence of AKI.Using current AKI definitions and classifications, the OPCAB technique for CABG, which avoids CPB; was associated with a significantly lower rate and less severe AKI compared to ONCAB. The OPCAB technique was identified as the only modifiable and potentially protective factor against postoperative AKI.

Hemodynamic shock (HS) is a clinical syndrome that is commonly observed in hospitalized patients. Prompt recognition and intervention are the cornerstones of mitigating the dire consequences of HS. Untreated HS usually leads to death. Unlike other types of clinical syndromes ( e.g. , chest pain), for which a clinical diagnosis is made before treatment is initiated in earnest, the treatment of shock often occurs concurrently or ahead of the diagnostic process. The maintenance of end-organ perfusion is critical to prevent irreversible organ injury and failure, and this frequently requires the use of fluid resuscitation and vasopressors. A complete review of all of the signs and symptoms, diagnosis, and treatment of HS has been reviewed in detail elsewhere (1). This article provides a concise summary of how to approach the patient in HS, diagnostic and therapeutic decision making, and the use of vasopressors. In addition, the effects of vasopressors on end organs with particular focus on renal hemodynamics is reviewed. HS is classically described as “an acute clinical syndrome initiated by ineffective perfusion, resulting in severe dysfunction of organs vital to survival” (1). As clinicians, we take great pains to teach our trainees that shock is not just hypotension, but that shock represents hypoperfusion of end organs. This rationale leads to the common refrain: “Normotensive patients can often suffer from shock.” The clinical manifestations of HS are related directly to the end organs that are not receiving adequate perfusion and can be categorized on the basis of the organ affected. Besides hypotension, the classic signs and symptoms of HS are tachycardia, relative hypotension (a decrease in baseline BP of 40 mmHg), tachypnea, cool and clammy extremities, oliguria, dysglycemia, and delirium (1). Patients who are hypotensive (systolic BP

Objectives: The ratio of the urinary mass concentrations of cystatin C and creatinine (UcysC/Ucrea) ≥ 11.3 mg/mmol has recently been proposed as an accurate marker for the detection of GFR ≤ 60 mL/min/1.73 m 2 . Design and methods: We prospectively evaluated the diagnostic performance of UcysC/Ucrea ≥ 11.3 mg/mmol and factors associated with increased UcysC/Ucrea in 72 children and adults with a wide variety of renal disorders. UcysC/Ucrea was calculated, and GFR wad estimated from serum creatinine and cystatin C by equations. Results: UcysC/Ucrea ≥ 11.3 mg/mmol had a low diagnostic value to detect GFR values ≤ 60 mL/min/1.73 m 2 estimated by creatinine or cystatin-C-based equations with sensitivities of 72% and 63%, and specificities of 42% and 34%. ROC curves for UcysC/Ucrea to detect GFR ≤ 60 mL/min/1.73 m 2 confirmed this with AUCs of 0.59 for creatinine and 0.57 for cystatin-C-based equations. Multivariate analysis identified tubular proteinuria, tubulointerstitial disease and heavy proteinuria, but not GFR ≤ 60 mL/min/1.73 m 2 , as factors independently associated with increased UcysC/Ucrea. Conclusions: UcysC/Ucrea ≥ 11.3 mg/mmol is not an accurate marker to detect GFR ≤ 60 mL/min/1.73 m 2 , but reflects tubular dysfunction and proteinuria due to heavy proteinuria and tubulointerstitial disease.

Peritoneal- und Hamodialyse werden als unterschiedliche, aber gleichwertige Dialyseverfahren angesehen. Fur die meisten Patienten sind aus medizinischer Sicht beide Verfahren gleichermasen geeignet. Wichtig fur die Auswahl ist der Wunsch des umfassend informierten Patienten. Die durch die Peritonealdialyse erreichten Moglichkeiten der Berufsausubung, Freizeitgestaltung, Reiseplanung und Unabhangigkeit haben fur viele Patienten einen hohen Stellenwert. Die Peritonealdialyse ist fur Kinder und fur Patienten mit Problemen mit der Hamodialyse zu bevorzugen und kontraindiziert bei aktiver oder intermittierender Divertikulitis. Erschwerte Bedingungen fur die Peritonealdialyse sind Erkrankungen mit erhohtem Peritonitisrisiko, Hernien, schwere obstruktive Lungenerkrankung, ausgepragter Eiweismangel und schwere Psychose. Falschlich angenommene Kontraindikationen sind Multimorbiditat, fortgeschrittenes Lebensalter, kardiovaskulare Erkrankungen, Transplantatversagen, Zystennieren und Anurie.

Use of potentially inappropriate medications may result in increased morbidity, mortality and resource utilisation. Due to polypharmacy and age-related decline in renal function the elderly population is at particular risk. Therefore, the Beers Criteria include use of nonsteroidal anti-inflammatory drugs in chronic renal failure stage 4 and 5 as these drugs may worsen renal function. According to the summary of product characteristics, the nonsteroidal anti-inflammatory drugs ibuprofen and diclofenac are contraindicated in these patients. Objective was to assess the extent of nonsteroidal anti-inflammatory drug use in nursing homes with a focus on residents with severe renal failure. Multi-centre cross-sectional study in 21 German nursing homes. The study population comprised residents for whom at least one serum creatinine value and information about sex were available, so that creatinine clearance rate could be estimated. In all, 685 of 852 residents were included as they fulfilled the abovementioned criteria. Renal failure was severe (estimated creatinine clearance rate

In Germany approximately 800,000 people are living in nursing homes. Outpatient medical treatment is provided by general practitioners (GP) and a variety of medical specialists. While nearly all residents have regular contact with GPs, care by specialists differs between the various disciplines.In this study an assessment of medical treatment for nursing home residents by GPs and specialists was made and compared with the available diagnoses.Between October 2014 and April 2015 a cross-sectional study was conducted in nursing homes in Bremen and the surrounding areas. Anonymized data based on residents' files were collated by nursing staff. Every contact with various specialists within the preceding 12 months was assessed and grouped into (a) no physician visit, (b) resident visited physician and (c) physician visited resident. Analyses were stratified for age, sex and level of care dependency as well as dementia and further comorbidities.A total of 852 residents in 21 nursing homes were included (mean age 83.5 years, 76.5 % female) in the study. Dementia was diagnosed in 57.7 %. Nearly all residents had had contact with their GP in the previous 12 months, mostly by home visits (96.9 %). The majority (54.5 %) had not seen a dentist in the preceding 12 months and 25.4 % had been visited by a dentist. Of the residents 47.4 % were visited by a neurologist or psychiatrist but only 4.5 % visited these specialists in their practice. Higher care dependency and younger age were associated with more frequent visits by neurologists and psychiatrists. Contact rates to ophthalmologists (29.3 %) and urologists (20.5 %) were less frequent. A diagnosis of diabetes mellitus had no influence on the contact rate with ophthalmologists.Medical care by specialists is characterized by huge variations. Besides a frequent contact rate with GPs there seems to be an undersupply regarding care by dentists and ophthalmologists.

Background Contrast media-induced nephropathy (CIN) is an increasing cause of hospital-acquired acute kidney injury and leads to a significant increase in mortality. There is uncertainty whether the use of iso-osmolar contrast media as opposed to the use of low-osmolar contrast media would be associated with a lower incidence of CIN. Therefore, we compared the nephrotoxicity of isoosmotic contrast media iodixanol with the low-osmotic contrast media iopromid in patients receiving contrast media during coronary angiography. Methods In this prospective double-blind study we examined 221 patients with normal renal function who received up to 1,000 ml of contrast media during coronary angiography, and compared the effect of iodixanol and iopromid on inducing contrast media nephropathy. Patients received 800 ml fluid orally before contrast media administration and 1,000 ml saline i.v. thereafter. Creatinine clearance, serum creatinine and urine-N-acetyl-beta-D-glucosaminidase (NAG) concentration was obtained 24 h before and 48 h after contrast media administration. Decrease of 20% of the creatinine clearance, increase of 25% of serum creatinine and increase of 20% of the urine concentration of NAG was defined as CIN. Results Incidence of CIN assessed by decreased creatinine clearance was 22.2% in the iopromid group and 19.7% in the iodixanol group. CIN defined by increased serum creatinine was 6.9% in the iopromid group and 8.6% in the iodixanol group. The difference between these two groups was not significant. Subgroup analysis of the diabetic patients or the patients that received high dose of contrast media revealed no significant difference in the incidence of CIN between the two contrast media. Conclusion The iso-osmolar and the low-osmolar contrast media exhibited the same incidence of CIN in our study population. If fluid administration is sufficient, the selection of either iopromid or iodixanol has no impact on the risk of developing CIN in patients with normal renal function, even when they are diabetic or receive a high dose of more than 500 ml contrast media.

Background. Acute myocardial infarction (AMI) has been reported and is associated with poor outcome in the course of thrombotic microangiopathies (TMA). However, data are very limited in regard to the clinical characteristics, risk factors and outcome of AMI during TMA. Furthermore, current AMI definitions based on troponins are more sensitive and specific to detect myocardial injury. Methods. We retrospectively analysed 74 consecutive patients with 78 TMA episodes. TMA was defined as platelets below 150 � 10 9 /l, haemolytic anaemia, elevated lactate dehydrogenase (LDH) and increased red cell fragmentation, and AMI as serum troponin I above 1 ng/ml with symptoms of myocardial ischaemia and/or appropriate electrocardiography (ECG) alterations. Results. AMI occurred in 14 TMA episodes (18%) (9 non- and 5 ST-segment elevation AMI). AMI occurred 5±3 days after TMA diagnosis, predominately in clinically suspected thrombotic thrombocytopenic purpura (TTP) as TMA subtype. Independent risk factors for subsequent AMI were TTP (RR 2.2; 95% CI 1.1–5.6), and serum LDH above 1000 U/l (RR 2.7; 95% CI 1.3–7.2) as well as serum troponin I above 0.20 ng/ml at TMA presentation (RR 13.5; 95% CI 2.6–86.8). LDH above 1000 U/l together with troponin I above 0.20 ng/ml had a sensitivity of 86% (95% CI 60–96%) and a specificity of 95% (95% CI 86–98%) to predict AMI in the later course of TMA. AMI contributed substantially to morbidity causing left ventricular dysfunction in three of eight survivors and potentially accounted for the death in five of six non-survivors. Conclusions. AMI is an early, frequent and severe complication during TMA. AMI occurs especially in TTP, and serum LDH above 1000 U/l in combination with serum troponin I above 0.20 ng/ml at TMA presentation are excellent predictors of subsequent AMI.

Early detection of acute renal failure by serum cystatin C. Background Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. Methods In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by ≥50% (R-criteria), by ≥100% (I-criteria), or by ≥200% (F-criteria). In analogy, ARF was detected when cystatin C increased by ≥50%, by ≥100%, or by ≥200%. Results Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by ≥50% 1.5 ± 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T 3 - or T 3 /T 4 syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. Conclusion Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine.

Background: Acute tubular necrosis (ATN) has high mortality, especially in patients who require renal replacement therapy (RRT). We prospectively studied the diagnostic accuracy of the urinary excretion of low-molecular-weight proteins and enzymes as predictors of a need for RRT in ATN.Methods: In 73 consecutive patients with initially nonoliguric ATN, we measured urinary excretion of α1- and β2-microglobulin, cystatin C, retinol-binding protein, α-glutathione S-transferase, γ-glutamyltransferase, lactate dehydrogenase, and N-acetyl-β-d-glucosaminidase early in the course of ATN.Results: Twenty-six patients (36%) required RRT a median of 4 (interquartile range, 2–6) days after detection of proteinuria and enzymuria. Patients who required RRT had higher urinary cystatin C and α1-microglobulin [median (interquartile range), 1.7 (1.2–4.1) and 34.5 (26.6–45.1) g/mol of creatinine] than patients who did not require RRT [0.1 (0.02–0.5) and 8.0 (5.0–17.5) g/mol of creatinine]. Urinary excretion of cystatin C and α1-microglobulin had the highest diagnostic accuracies in identifying patients requiring RRT as indicated by the largest areas under the ROC curves: 0.92 (95% confidence interval, 0.86–0.96) and 0.86 (0.78–0.92), respectively. Sensitivity and specificity were 92% (95% confidence interval, 83–96%) and 83% (73–90%), respectively, for urinary cystatin C >1 g/mol of creatinine, and 88% (78–93%) and 81% (70–88%) for urinary α1-microglobulin >20 g/mol of creatinine.Conclusion: In nonoliguric ATN, increased urinary excretion of cystatin C and α1-microglobulin may predict an unfavorable outcome, as reflected by the requirement for RRT.

Background: Urinary excretion of the low molecular weight protein cystatin C is a marker of renal disorders and a good predictor of the severity of acute tubular necrosis. We evaluated the measurement of urinary cystatin C and determined its reference range. Methods: Measurement of urinary cystatin C by particle-enhanced nephelometric immunoassay (PENIA) in 102 patients with various renal disorders and 133 healthy controls. We assessed the influence of pH and temperature, interferences on urinary cystatin C measurement, as well as cystatin C adsorption to plastic. Results: The upper reference value for urinary cystatin C was 0.28 mg/L, independent of age and gender. Accuracy and linearity ( r2=0.996) were excellent. Intra- and inter-assay precision were ≤4.8% and ≤5.2%, respectively. Albumin (≤160 g/L), bilirubin (≤500 µmol/L) and haemoglobin (≤210 µmol/L) did not show interferences. Urinary cystatin C was stable, at urine pH≥5, at -20°C and 4°C for 7 days, and at 20°C for 48 h. Freezing and thawing did not influence urinary cystatin C concentration. There was no adsorption of cystatin C to plastic. Conclusion: Urinary cystatin C measurement by PENIA is precise. High stability and no interference add to the practicability of urinary cystatin C as a routine biochemical test.

Progress in treating human acute renal failure (ARF) is dependent on developing techniques that allow for the rapid diagnosis, quantification of injury, further understanding of the pathophysiology, and the effects of therapy. Therefore, four techniques that will facilitate this progress are described and illustrated by four different investigative teams. Techniques to measure rapid changes in GFR are available for rapid diagnosis and quantification of ARF in humans. State-of-the-art magnetic resonance imaging (MRI) presently allows for enhanced resolution of regional renal blood flow and functional evaluations in patients. Furthermore, new probes and techniques for MRI that allow for identification and quantitation of inflammation, applicable to human ARF, are being developed and tested in animal models. Finally, two-photon microscopy will allow for four-dimensional cellular and subcellular studies in animal models of ARF providing rapid insights into pathophysiology and the therapeutic effects of a variety of promising agents. Further development and utilization of these techniques, especially in concert with genetic, proteomic, and molecular approaches, will allow for needed insights into the pathophysiology and therapy in human ARF.

Disruption of the actin cytoskeleton in proximal tubule cells is a key pathophysiological factor in acute renal failure. To investigate dynamic alterations of the actin cytoskeleton in live proximal tubule cells, LLC-PK10cells were transfected with an enhanced yellow fluorescence protein (EYFP)-actin construct, and a clone with stable EYFP-actin expression was established. Confluent live cells were studied by confocal microscopy under physiological conditions or during ATP depletion of up to 60 min. Immunoblots of stable transfected LLC-PK10cells confirmed the presence of EYFP-actin, accounting for 5% of total actin. EYFP-actin predominantly incorporated in stress fibers, i.e., cortical and microvillar actin as shown by excellent colocalization with Texas red phalloidin. Homogenous cytosolic distribution of EYFP-actin indicated colocalization with G-actin as well. Beyond previous findings, we observed differential subcellular disassembly of F-actin structures: stress fibers tagged with EYFP-actin underwent rapid and complete disruption, whereas cortical and microvillar actin disassembled at slower rates. In parallel, ATP depletion induced the formation of perinuclear EYFP-actin aggregates that colocalized with F-actin. During ATP depletion the G-actin fraction of EYFP-actin substantially decreased while endogenous and EYFP-F-actin increased. During intracellular ATP repletion, after 30 min of ATP depletion, there was a high degree of agreement between F-actin formation from EYFP-actin and endogenous actin. Our data indicate that EYFP-actin did not alter the characteristics of the endogenous actin cytoskeleton or the morphology of LLC-PK10cells. Furthermore, EYFP-actin is a suitable probe to study the spatial and temporal dynamics of actin cytoskeleton alterations in live proximal tubule cells during ATP depletion and ATP repletion.

Background Infection results in considerable morbidity and mortality in haemodialysis patients. Diagnosis of infection can be difficult because currently applied laboratory parameters may be non-specifically altered due to uraemia or haemodialysis (HD). This study investigated the diagnostic value and kinetics of serum procalcitonin (PCT), a low-molecular-weight protein, in patients receiving intermittent HD. Methods Sixty-eight patients receiving intermittent HD for end-stage renal disease (n=48) or acute renal failure (n=20) were prospectively studied, 47 treated with high-flux and 21 with low-flux membranes. Of 36 patients with severe infections or sepsis, 27 were treated with high-flux and nine with low-flux membranes. WBC, serum PCT and C-reactive protein (CRP) concentrations were measured immediately before HD, and PCT repeatedly during the following 48 h. Results When determined immediately before HD, PCT demonstrated a sensitivity of 89%, a specificity of 81%, and positive and negative predictive values of 84 and 87%, indicating severe infection or sepsis. These levels were higher than the respective values for CRP (89, 48, 68 and 78%) and WBC (58, 75, 71 and 59%). After 4 h of HD with high-flux membranes, PCT decreased significantly to 83+/-25% and did not return to predialysis concentrations before 48 h. This decrease in serum PCT resulted in markedly reduced sensitivity (65%) and negative predictive value (54%). In contrast, no marked change in PCT concentration occurred during or after HD with low-flux membranes. Conclusion Serum PCT is an accurate indicator of severe infection and sepsis in patients receiving intermittent HD. High-flux membranes substantially decrease PCT. When utilizing high flux membranes, serum PCT concentrations should be determined prior to the start of HD.

Following bone marrow transplantation, acute renal failure and proteinuria are common complications with a high mortality, particularly in patients requiring hemodialysis. Incidence, potential predisposing factors, and outcome of acute renal complications in patients with hematological malignancies receiving autologous peripheral blood stem cell transplantation were prospectively studied in 53 patients. Eight patients developed acute renal failure. Three of them required hemodialysis. Of all patients with acute renal failure, only those requiring hemodialysis died, due to nonrenal causes. Only 1 of the 45 patients without renal failure died. Mild proteinuria of predominantly tubular origin occurred in 16 patients, in 3 with and in 13 without acute renal failure. As predisposing factors for acute renal failure were identified: renal hypoperfusion due to systemic inflammatory response syndrome, sepsis or septic shock, and combined administration of nephrotoxic drugs. Especially those patients receiving high numbers of nephrotoxic drugs in combination with renal hypoperfusion were likely to develop acute renal failure. These results suggest that patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation have a low risk of developing acute renal failure and proteinuria.

We have studied activation of mitogen-activated protein kinase (MAP kinase) and [3H]-thymidine uptake as a marker for cellular proliferation in a proximal tubular cell line of the American Opossum kidney (OK cells). Adrenaline, serotonin, epidermal growth factor and insulin all stimulated MAP kinase and [3H]-thymidine uptake. This stimulation of cellular proliferation was markedly reduced by an inhibitor of the MAP kinase pathway, PD 98059. Epidermal growth factor stimulated MAP kinase activity more effectively than the other agonists, but all four had similar effects on OK cellular proliferation. These data indicate that amine neurotransmitters may be of similar importance for tubular regeneration as classical growth factors.

Objective To determine the incidence and prevalence of CKD and of progressive GFR decline, to identify modifiable risk factors of and to develop a predictive risk model for progressive GFR decline in high risk primary care patients. Methods Retrospective observational study of 803 patients with or at high risk of CKD exclusively managed in primary care. Baseline data was collected in 2003, follow-up data in 2006. High risk was defined as inadequately controlled hypertension or diabetes, and GFR 2.5 ml min − 1 1.73 m − 2 . Results CKD was present in 25.4% at baseline and developed in further 13.7% during follow-up, 42.5% demonstrated progressive GFR decline. Obesity, proteinuria, heart failure, inadequate hypertension and diabetes control, lacking angiotensin-converting-enzyme-inhibitors or angiotensin-receptor-blockers, radio contrast, and dual renin–angiotensin-aldosterone-system blockade were identified as modifiable, independent risk factors of progressive GFR decline. The risk model, containing 7 readily obtainable variables, showed good discriminative ability. Conclusions High risk primary care patients demonstrated high CKD prevalence and incidence, and rate of progressive GFR decline. Identified risk factors can be modified in primary care. Our risk model may aid primary care physicians to predict patients at high risk of progressive GFR decline.

To study the frequency, severity, and long-term outcome of renal injury in Cortinarius orellanus poisoning, to evaluate the association between the ingested amount of C. orellanus and outcome, and to evaluate the effect of N-acetylcysteine and corticosteroid treatment on outcome.Case series of eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic kidney disease (CKD) were classified according to current AKI and CKD definitions. N-acetylcysteine and corticosteroids were administered to six patients, former according to the standard for paracetamol poisoning.All patients developed AKI, six in the most severe stage and four required renal replacement therapy (RRT). After 12 months, seven patients presented with CKD, of whom three required chronic RRT and further two were in advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of Cortinarius orellanus (r = 0.98, p 0.001 and r = 0.78, p = 0.02, respectively) but not with N-acetylcysteine and corticosteroid treatment.AKI and CKD by current definitions and classifications are frequent and severe after Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus correlates with the severity of both AKI and CKD. N-acetylcysteine and corticosteroid treatment do not seem to have a beneficial effect on either AKI or CKD.