Update to the study protocol: minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): a multicentre, stepped-wedge, cluster-randomised controlled trial.

This document reports a brief update to the previously published protocol of the MinDial study.Trial registration German Clinical Trials Register DRKS00029691. Registered on 12 Sept. 2022, https://drks.de/search/en/trial/DRKS00029691 .

Minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): study protocol for a multicentre, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. METHODS: The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. DISCUSSION: This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.

[Central venous catheters as access for acute and long-term dialysis]. / Zentralvenöse Katheter als Zugang für die Akut- und Dauerdialyse.

Central venous dialysis catheters are indispensible as a rapid large lumen access to the blood compartment. If such a central venous catheter is necessary for longer than 2-3 weeks it is better to implant a tunnelled cuffed catheter initially or to switch early from the non-tunnelled acute catheter to a tunnelled cuffed catheter. Tunnelled cuffed catheters can be used for many weeks or even years and the complication rate is less than that of non-tunnelled acute catheters. The proportion of dialysis patients with long-term dialysis using tunnelled cuffed catheters has increased rapidly in recent years and now stands at approximately 20 % in Germany. These catheters are, however, prone to more infectious complications and more thromboses than native arteriovenous fistulas or prosthetic shunts. The mortality of patients with long-term dialysis catheters is also higher than those with arteriovenous shunts. For these reasons central venous catheters will always be regarded as the third choice dialysis access when arteriovenous fistulas are not possible. Catheters are available in a wide variety of designs but the individual advantages are still unclear. In order to avoid short-term and long-term complications a variety of measures for implantation and use during dialysis treatment have been developed which make the use safer.

Multidisciplinary management of vascular access for haemodialysis: from the preparation of the initial access to the treatment of stenosis and thrombosis.

In February 2008 a multidisciplinary study group was established in Germany to improve the treatment of patients with potential vascular access problems. As one of the first results of their work interdisciplinary recommendations for the management of vascular access were provided, from the creation of the initial access to the treatment of complications. As a rule the wrist arteriovenous fistula (AVF) is the access of choice due to its lower complication rate when compared to other types of access. The AVF should be created 3 months prior to the expected start of haemodialysis to allow for sufficient maturation. Second and third choice accesses are arteriovenous grafts (AVG) and central venous catheters (CVC). Ultrasound is a reliable tool for vessel selection before access creation, and also for the diagnosis of complications in AVF and grafts. Access stenosis and thrombosis can be treated surgically and interventionally. The comparison of both methods reveals advantages and disadvantages for each. The therapeutic decision should be based on the individual patients' constitution, and also on the availability and experience of the involved specialists.

How does late nephrological co-management impact chronic kidney disease? - an observational study.

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 < 0.01). Inadequate control of blood pressure, anaemia, volume status, malnutrition and emergency initial dialysis, but not LR itself were independently associated with mortality. CONCLUSIONS: Late referral was associated with a substantially lower survival after correction for lead-time and immortal time bias and with inferior control of most risk factors for CKD progression, complications and cardiovascular risk factors. CKD patients may particularly profit from adequate control of blood pressure, anaemia, nutritional and volume status, and avoidance of emergency initial dialysis as these factors may predominately contribute to survival.

Use of LifeSite port systems for hemodialysis in Germany.

AIM: Studies haveshown lower infection rates of port systems compared to established, transcutaneous cuffed-tunneled dialysis catheters. This was shown in otherwise quite healthy patients starting hemodialysis treatment. It is unclear to what extent these results can be applied to countries such as Germany where, unlike the US, central venous access systems are used mainly for patients with a high comorbidity. We investigated complications in patients with exhausted access sites and a high comorbidity. METHOD: In a retrospective, representative multicenter study, 34 patients with a high rate of comorbidity were assessed. The age was 67.5 +/- 12.5 years, the median number of failed AV fistulas or AV grafts was 4 (0-18). RESULTS: The survival rate was 84.9%, 55.2% and 55.2% after 6, 12 and 24 months, respectively. The rate of local and systemic infections was 2.83 per 1,000 patient days. Thrombotic events occurred at a rate of 2.26 per 1,000 patient days. We did not see a statistically significant effect using 0.2% sodium oxychlorosene (n = 13) or 70% isopropyl alcohol solution (n = 21) as the antimicrobial solution used before opening the valve of the port with the dialysis needle. CONCLUSIONS: We showed that complications of hemodialysis treatment using LifeSite vascular access systems in patients with very high co-morbidity in Germany seem to occur less often than those reported for cuffed-tunneled catheters and were not more frequent than those reported for other patient groups using LifeSites in the US. Technical survival rates were encouraging for up to two years. LifeSite port systems might be a good or even better central venous access than cuffed-tunneled catheters for patients in which an AV fistula or -graft is not possible.

Successful treatment of renovascular hypertension has no effect on insulin sensitivity.

BACKGROUND: The association of insulin resistance (IR) and essential hypertension is well known, but a causal relationship has not been proven. Patients with secondary hypertension as a result of renal artery stenosis (RAS) usually do not reveal IR, but no study has addressed the effect of blood pressure reduction after successful treatment of RAS on insulin sensitivity and glucose effectiveness. PATIENTS AND METHODS: The insulin sensitivity index (SI) and glucose effectiveness (SG) were measured before and after successful intervention of an angiographically proven significant RAS in 18 out of 23 patients (eight males/10 females; mean age 51.5 +/- 13.1 years) in which improvement/cure of arterial hypertension was achieved. After a mean of 10.7 months, patients were reevaluated for 24-h blood-pressure measurement, kidney function, adrenaline, noradrenaline, plasma-renin-activity (PRA), aldosterone, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), and glucose metabolism parameters such as basal insulin, glucose disappearance constant (K-value), SI and SG. For calculation of SI and SG, insulin and glucose data from the modified frequent sampling intravenous glucose tolerance test (FSIGT) were submitted to the MINMOD program. RESULTS: After intervention, systolic 24-h blood pressure had decreased from 156.1 +/- 16.4 mmHg to 139.9 +/- 15.1 mmHg, and diastolic 24-h blood pressure from 97.1 +/- 14.7 mmHg to 87.3 +/- 13.4 mmHg. No significant change in SI (before 4.3 +/- 2.0, after 4.8 +/- 2.0 min(-1) per microU mL(-1)) or SG (before 1.55 +/- 0.42x10(-2) min(-1), after 1.8 +/- 0.48x10(-2) min(-1)) was observed. Aldosterone decreased from 246.7 +/- 180.7 to 115 +/- 61.4 (P=0.009) as PRA decreased from 12.4 +/- 11.4 to 4.2 +/- 7.6 ng mL h(-1) (P=0.01). Creatinine clearance, and adrenaline and noradrenaline levels as well as ANP and cGMP did not change after treatment for RAS. Subsequent to the definition of IR (SI < or =3.2x10(-4) min(-1) per microU mL(-1)) some differences among these two subgroups (SI < or =3.2, or SI>3.2) could be found. Patients with IR (n=8) were characterized by a higher body mass index (BMI), higher basal insulin values and significantly lower cGMP values. Only the group without IR (n=10) developed significant improvement of systolic blood pressure. CONCLUSION: We conclude that blood pressure reduction by treatment of RAS does not alter insulin action and that there is no link between the circulating concentrations of renin/aldosterone and glucose metabolism in renovascular hypertension (RVH). The results do not support the hypothesis of a direct link between blood pressure in RVH and the individual state of insulin sensitivity. However, patients with a normal SI are more likely to experience an almost normalization of arterial blood pressure after treatment for RAS.

Noninvasive investigation for renal artery stenosis: contrast-enhanced magnetic resonance angiography and color Doppler sonography as compared to digital subtraction angiography.

INTRODUCTION: The question about the most appropriate non-invasive method for detecting a renal artery stenosis (RAS) when comparing contrast enhanced magnetic resonance angiography (MRA) and color Doppler sonography (CDS) is still under discussion. Therefore we conducted a prospective study in order to evaluate both methods as compared to digital subtraction angiography (DSA). PATIENTS/METHODS: Thirtysix consecutive patients (53,9 +/- 13,7 years) with suspected RAS were investigated. MRA was performed using gadolinium for contrast enhancement. CDS was performed using a 2.5 and 3,5 MHz transducer. A peak systolic velocity (Vmax) >200 cm/sec within renal arteries and/or a side to side difference of the resistive index (RI) of >0,05 were used to discriminate stenosis. A diameter reduction of > or = 60% by DSA was considered a stenosis relevant to the patient. RESULTS: Sixty-eight main renal arteries and 9 accessory vessels were detected by DSA. Twenty main and 3 accessory arteries were found to be stenosed > or = 60%, while 4 main and 1 accessory artery presented with occlusion. MRA detected 70 renal vessels (65 main and 5 accessory arteries). Twenty-one stenosed arteries and 4 occluded vessels were correctly diagnosed by MRA. With CDS 68 renal vessels (62 main and 6 accessory arteries) could be visual- ized out of which 21 stenoses were diagnosed because of increased Vmax and 6 stenoses were detected because of a side to side difference of RI. For main renal arteries sensitivities and specificities were 96% and 86% for MRA and 96% and 89% for CDS. CONCLUSIONS: MRA and CDS are both comparable methods for detection of a renal artery stenosis > or = 60%. Despite several limitations, CDS can at the moment still be favored as a screening method.

Assessment of radiocontrast media induced renal vasoconstriction by color coded duplex sonography.

INTRODUCTION: Changes in renal hemodynamics are suspected to be one of the major pathogenetic correlates in radiocontrast media-induced nephrotoxicity. We investigated whether color-coded duplex sonography is an appropriate method to document changes in intrarenal vascular resistance, after intravenous injection of the low-osmolar contrast material lopamidol. METHODS: Intrarenal arterial doppler wave forms were analyzed every minute after intravenous injection of 100 mL lopamidol in 10 patients during a voiding cystourogram-procedure. The Resistive Index (RI) of each flow curve, reflecting intrarenal flow resistance, was calculated and compared to the mean of four RI measurements taken before contrast media application. RESULTS: One minute after injection of Iopamidol the RI remained unchanged compared to the baseline standard of 0.70. In measurements obtained 2, 3, 4, and 5 minutes after lopamidol injection a statistically significant rise was seen: (minute 2: 0.74, p < 0.001/minute 3: 0.75, p = 0.001/minute 4: 0.72, p =0.018/minute 5: 0.74, p = 0.031). During the further course, the resistive indices decreased progressively and showed no significant difference in comparison with the baseline standard value. CONCLUSION: Color coded duplex sonography is a simple method to detect changes in renal flow resistance after application of radiocontrast media. Based on our results, we believe that the analysis of intrarenal arterial doppler flow profiles constitutes an ideal method to investigate pathophysiologic mechanisms of radiocontrast media-induced nephrotoxicity, as well as pharmacological concepts in nephroprotectivity.

Effect of acute intravenous ace-inhibition on the intrarenal doppler flow characteristics in hypertensive patients with and without unilateral renal artery stenosis.

Assessment of intrarenal doppler signals is of particular importance in screening for renal artery stenosis. We studied the effect of acute ACE-inhibition (1,25 mg enalaprilate i.v.) on intrarenal resistive indices in 10 hypertensive patients with unilateral renal artery stenosis versus 10 patients with essential hypertension. Any changes limited to poststenotic vessels could possibly improve the diagnostic value of duplex sonography. After ACE-inhibition a significant fall of the intrarenal Resistive Index occurred in both patient groups. In cases of unilateral renal artery stenosis we saw a tendency to an increased side difference of the Resistive Index due to a greater fall on the poststenotic side. Therefore a clear advantage of duplex scanning after acute ACE-inhibition due to a limited effect of enalaprilate on poststenotic vessels was not found. The results suggest that the vascular resistance and not only the degree of renal artery stenosis is of significance for the characteristics of the doppler signal.

Congestive heart failure as an indication for continuous renal replacement therapy.

Continuous venovenous hemofiltration (CVVH) is the most widely used renal replacement therapy for the treatment of critically ill patients with acute renal failure on the intensive care unit. Whether or not congestive heart failure is an indication for CVVH is controversial and needs to be discussed. Therefore, we present a patient with congestive heart failure who was treated successfully with CVVH.

Percutaneous renal biopsy: three years of experience with the biopty gun in 761 cases--a survey of results and complications.

From 1.1.1993 to 12.31.1995 we performed 761 consecutive biopsies on 509 non-selected patients. The most frequent diagnoses in 351 biopsies (39.4%) on native kidneys were 262 cases of glomerulonephritis (74.6%) and 167 of so-called benign nephrosclerosis (47.6%). With 410 biopsies (60.6%) on allograft kidneys 219 cases (78%) showed signs of interstitial rejection, 14 cases (5%) vascular and 49 cases (17%) interstitial as well as vascular rejection. Only after 5 biopsies (0.66%) clinical relevant complications (3 perirenal haematomas, 1 AV fistula, 1 vesical tamponade) appeared. Again percutaneous renal biopsy is proven to be a diagnostically efficient and safe tool at the same time even when used in a large number of non-selected patients, so that an ambulant performance may be discussed. The relatively frequent diagnosis of a so-called benign nephrosclerosis seems to indicate the need for an intensified examination of this disease.

Haemolytic-uraemic syndrome and thrombotic-thrombocytopenic purpura in adults: clinical findings and prognostic factors for death and end-stage renal disease.

BACKGROUND: Left untreated, haemolytic-uraemic syndrome (HUS) and thrombotic-thrombocytopenic purpura (TTP) in adults have a poor prognosis with mortality rates reaching 90%. Patients who survive often develop end-stage renal disease. Because of similarities in clinical and morphological findings, both diseases are considered as one entity referred to as HUS-TTP syndrome. METHODS: From 1974 to January 1995, 45 adult patients received treatment for HUS-TTP at our clinic. By stepwise logistic regression analyses, we examined how known risk factors and plasma exchange with fresh-frozen plasma (PE) influenced mortality and end-stage renal disease. RESULTS: Three of 45 patients died (7%). Though we were not able to find significant predictors of mortality, low haemoglobin levels (5.93 +/- 0.32 vs 9.10 +/- 2.16 g/dl) and high leukocyte counts on admission (15.830 +/- 3.690 vs 11.150 +/- 4.580 microliters-1) appeared to indicate an unfavourable outcome. Regarding the development of end-stage renal disease, PE proved to be the only favourable indicator (P = 0.0001). PE was performed in 30 patients 3-20 times (9.2 +/- 4.8, mean +/- SD). Of 28 surviving patients treated with PE, only four developed end-stage renal disease, whereas dialysis was necessary in 11 of 14 patients not treated with PE. Application of PE led to an 81.8% reduction of the relative risk of developing end-stage renal disease. An additional prognostic influence of other potential risk factors such as age, sex, platelet count on admission, lactate dehydrogenase serum levels, serum creatinine, blood pressure, prodromal disease, and renal histology was not found. CONCLUSION: This retrospective clinical study confirms the therapeutic value of plasma exchange with fresh-frozen plasma to maintain renal function in patients with HUS-TTP.

Development of insulin resistance and elevated blood pressure during therapy with cyclosporine A.

OBJECTIVES: Essential hypertension and insulin resistance frequently coexist; cyclosporine A (CsA) is known to induce hypertension which has been used as a model for essential hypertension. The present study aimed to evaluate whether elevated blood pressure and insulin resistance coexist during CsA therapy to prove the similarity between essential hypertension and CsA induced hypertension. DESIGN: Normotensive patients who underwent keratoplasty were investigated before and during single therapy with CsA (2-4 mg/kg body weight) in an open A-B Trial. PATIENTS: Eighteen lean, normotensive patients without metabolic disorders with normal renal function and without family history of hypertension or metabolic abnormalities. MAIN METHODS: Insulin sensitivity index was determined by the modified frequent sampling intravenous glucose tolerance test (FSIGT) and blood pressure was determined by indirect ambulatory blood pressure monitoring. RESULTS: Mean insulin sensitivity index (S1) was significantly reduced (p < 0.03) during treatment with CsA (4.4 +/- 2.6 x 10(-4) vs 2.8 +/- 2.0 x 10(-4)/min per microU/ml), whereas mean systolic daytime blood pressure increased from 126.4 +/- 10.8 mmHg to 135.7 +/- 11.8 mmHg (p < 0.02), as well as the corresponding diastolic blood pressure from 76.8 +/- 8.7 mmHg to 82.8 +/- 9.3 mmHg (p < 0.05). CONCLUSIONS: CsA therapy induces elevated blood pressure and insulin resistance as seen in patients with essential hypertension, thus CsA induced hypertension is considered to have pathophysiological similarities to essential hypertension.

[Doppler sonographic evaluation of the effectiveness of an antirejection treatment after kidney transplantation]. / Dopplersonographische Beurteilung der Effektivität einer Abstossungstherapie nach Nierentransplantation.

Data on 64 rejection reactions in 108 consecutive patients after renal transplantation (61 males, 47 females; mean age 42.8 +/- 12.9 years) were analysed to test what Doppler sonographic measurements can be used to predict whether a given drug regimen is able to suppress rejection. Results were compared with renal function and histological evidence of rejection. The >> pulsatility index << (PI), which is dependent on flow resistance, was determined by Doppler echocardiography: it increases on rejection (measurements made 2.0 +/- 1.1 days apart). The rejection reaction was successfully controlled by drugs (methylprednisolone, azathioprine and cyclosporin) in 44 patients (group 1), but not in 20 patients (group 2). PI before rejection (group 1: 1.8 +/- 0.5; group 2: 1.7 +/- 0.6), PI during histologically confirmed rejection (2.6 +/- 1.2 and 3.1 +/- 1.4, respectively), the size of difference between these values, and parameters of renal function provided no pointers to any drug efficacy in suppressing rejection. But individual changes in PI during suppression treatment proved to be of outstanding value (P < 0.00005). Signs of florid rejection at the end of treatment period correlated with a rising PI in 13 of 17 rejection episodes, while PI fell in only 7 of 47 episodes. Vascular signs of rejection tended to be poor predictors of rejection (P .028). - These findings indicate that serial Doppler sonography can be helpful in monitoring antirejection treatment.