Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so ...that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries.
All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data.
This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100,000/year for membrano-proliferative GN, 0.2/100,000/year for mesangio-proliferative GN, 0.6/100,000/year for minimal change disease, 0.8/100,000/year for focal segmental glomerulosclerosis, 1.2/100,000/year for membranous nephropathy and 2.5/100,000/year for IgA nephropathy. Rates were lower in children at around 0.1/100,000/year with the exception of minimal change disease where incidence was reported to be 2.0/100,000/year in Caucasian children with higher rates in Arabian children (9.2/100,000/year) and Asian children (6.2-15.6/100,000/year).
This study found that incidence rates of primary GN vary between 0.2/100,000/year and 2.5/100,000/year. The incidence of IgA nephropathy is at least 2.5/100,000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found.
Abstract
Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. ...However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death adjusted hazard ratio (aHR) 0.89, but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. Increased circulating vasopressin (AVP) concentrations are supposed to play a role in the ...progression of ADPKD. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with consequently an enhanced AVP response to water deprivation with higher circulating AVP concentrations.
15 ADPKD (eGFR<60) patients and 15 age-, sex- and eGFR-matched controls with IgA nephropathy (IgAN), underwent a water deprivation test to determine maximal urine concentrating capacity. Plasma and urine osmolality, urine aquaporin-2 (AQP2) and plasma AVP and copeptin (a surrogate marker for AVP) were measured at baseline and after water deprivation (average 16 hours). In ADPKD patients, height adjusted total kidney volume (hTKV) was measured by MRI.
Maximal achieved urine concentration was lower in ADPKD compared to IgAN controls (533±138 vs. 642±148 mOsm/kg, p = 0.046), with particularly a lower maximal achieved urine urea concentration (223±74 vs. 299±72 mmol/L, p = 0.008). After water deprivation, plasma osmolality was similar in both groups although change in plasma osmolality was more profound in ADPKD due to a lower baseline plasma osmolality in comparison to IgAN controls. Copeptin and AVP increased significantly in a similar way in both groups. AVP, copeptin and urine AQP2 were inversely associated with maximal urine concentrating in both groups.
ADPKD patients have a more severely impaired maximal urine concentrating capacity with a lower maximal achieved urine urea concentration in comparison to IgAN controls with similar endogenous copeptin and AVP responses.
Ultrafiltration (UF) of excess fluid activates numerous compensatory mechanisms during hemodialysis (HD). The increase of both total peripheral and splanchnic vascular resistance is considered ...essential in maintaining hemodynamic stability. The aim of this study was to evaluate the extent of UF-induced changes in hepato-splanchnic blood flow and resistance in a group of maintenance HD patients during regular dialysis.
Hepato-splanchnic flow resistance index (RI) and hepato-splanchnic perfusion index (QI) were measured in 12 chronic HD patients using a modified, non-invasive Indocyaningreen (ICG) dilution method. During a midweek dialysis session we determined RI, QI, ICG disappearance rate (kICG), plasma volume (Vp), hematocrit (Hct), mean arterial blood pressure (MAP) and heart rate (HR) at four times in hourly intervals (t1 to t4). Dialysis settings were standardized and all patient studies were done in duplicate.
In the whole study group mean UF volume was 1.86 ± 0.46 L, Vp dropped from 3.65 ± 0.77L at t1 to 3.40 ± 0.78L at t4, and all patients remained hemodynamically stable. In all patients RI significantly increased from 12.40 ± 4.21 mmHg∙s∙m2/mL at t1 to 14.94 ± 6.36 mmHg∙s∙m2/mL at t4 while QI significantly decreased from 0.61 ± 0.22 at t1 to 0.52 ± 0.20 L/min/m2 at t4, indicating active vasoconstriction. In diabetic subjects, however, RI was significantly larger than in non-diabetics at all time points. QI was lower in diabetic subjects.
In chronic HD-patients hepato-splanchnic blood flow substantially decreases during moderate UF as a result of an active splanchnic vasoconstriction. Our data indicate that diabetic HD-patients are particularly prone to splanchnic ischemia and might therefore have an increased risk for bacterial translocation, endotoxemia and systemic inflammation.
Vancomycin is frequently used in hemodialysis (HD) and in hemodiafiltration (HDF) patients and is usually administered in the last 30 or 60 minutes of a dialysis session. Vancomycin pharmacokinetics ...are not well described in HDF patients. The aim of this study is to develop a population pharmacokinetic (PPK) model and dosing regimen for vancomycin in HDF patients and to evaluate its applicability in low-flux (LF-HD) patients.
Two-compartment PPK models were developed using data from HDF patients (n = 17), and was parameterized as follows: non-renal clearance (CLm), renal clearance as a fraction of creatinine clearance (fr), central volume of distribution (V1), intercompartmental clearance (CL12), peripheral volume of distribution (V2) and extracorporeal extraction ratio (Eec). We evaluated the final model in a cohort of LF-HD patients (n = 21). Dosing schemes were developed for a vancomycin 24-h AUC of 400 mg*h/L.
Model parameters (± SD) were: CLm = 0.473 (0.271) L/h, fr = 0.1 (fixed value), V1 = 0.278 (0.092) L/kgLBMc, CL12 = 9.96 L/h (fixed value), V2 = 0.686 (0.335) L/kgLBMc and Eec = 0.212 (0.069). The model reliably predicted serum levels of vancomycin in both HDF and LF-HD patients during and between dialysis sessions. The median of the prediction error (MDPE) as a measure of bias is -0.7% (95% CI: -3.4%-1.7%) and the median of the absolute values of the prediction errors (MDAPE) as a measure of precision is 7.9% (95% CI: 6.0%-9.8%). In both HDF and LF-HD, the optimal vancomycin loading dose for a typical patient weighing 70 kg is 1700 mg when administered during the last 60 minutes of the hemodialysis session. Maintenance dose is 700 mg if administered during the last 30 or 60 minutes of the hemodialysis session.
The developed PPK model for HDF is also capable of predicting serum levels of vancomycin in patients on LF-HD. A dosing regimen was developed for the use of vancomycin in HDF and LF-HD.
Significant advances have lead to a greater understanding of the role of the complement system within nephrology. The success of the first clinically approved complement inhibitor has created renewed ...appreciation of complement-targeting therapeutics. Several clinical trials are currently underway to evaluate the therapeutic potential of complement inhibition in renal diseases and kidney transplantation. Although, complement has been known to be activated during dialysis for over four decades, this area of research has been neglected in recent years. Despite significant progress in biocompatibility of hemodialysis (HD) membranes and peritoneal dialysis (PD) fluids, complement activation remains an undesired effect and relevant issue. Short-term effects of complement activation include promoting inflammation and coagulation. In addition, long-term complications of dialysis, such as infection, fibrosis and cardiovascular events, are linked to the complement system. These results suggest that interventions targeting the complement system in dialysis could improve biocompatibility, dialysis efficacy, and long-term outcome. Combined with the clinical availability to safely target complement in patients, the question is not if we should inhibit complement in dialysis, but when and how. The purpose of this review is to summarize previous findings and provide a comprehensive overview of the role of the complement system in both HD and PD.
Background: Intradialytic hypotension (IDH) is considered to be a frequent complication of hemodialysis (HD) and is associated with symptom burden, increased incidence of access failure, ...cardiovascular events, and higher mortality. This systematic literature review aims to analyse studies that investigated the prevalence of IDH. A complicating factor herein is that many different definitions of IDH are used in literature. Methods: A systematic literature search from databases, Medline, Cinahl, EMBASE, and the Cochrane library to identify studies reporting on the actual prevalence of IDH was conducted. Studies were categorized by the type of definition used for the prevalence of IDH. A meta-analysis of the prevalence of IDH was performed. Results: In a meta-analysis comprising 4 studies including 1,694 patients and 4 studies including 13,189 patients, the prevalence of HD sessions complicated by IDH was 10.1 and 11.6% for the European Best Practice Guideline (EBPG) definition and the Nadir <90 definition, respectively. The proportion of patients with frequent IDH could not reliably be established because of the wide range in cutoff values that were used to identify patients with frequent IDH. There was a large variety in the prevalence of symptoms and interventions. Major risk factors associated with IDH across studies were diabetes, a higher interdialytic weight gain, female gender, and lower body weight. Conclusion: Our meta-analysis suggests that the prevalence of IDH is lower than 12% for both the EBPG and the Nadir <90 definition which is much lower than stated in most reviews.
Near-infrared spectroscopy (NIRS) is used to monitor cerebral tissue oxygenation (rSO2) depending on cerebral blood flow (CBF), cerebral blood volume and blood oxygen content. We explored whether ...NIRS might be a more easy applicable proxy to 15OH2O positron emission tomography (PET) for detecting CBF changes during hemodialysis. Furthermore, we compared potential determinants of rSO2 and CBF. In 12 patients aged ≥ 65 years, NIRS and PET were performed simultaneously: before (T1), early after start (T2), and at the end of hemodialysis (T3). Between T1 and T3, the relative change in frontal rSO2 (ΔrSO2) was −8 ± 9% (P = 0.001) and −5 ± 11% (P = 0.08), whereas the relative change in frontal gray matter CBF (ΔCBF) was −11 ± 18% (P = 0.009) and −12 ± 16% (P = 0.007) for the left and right hemisphere, respectively. ΔrSO2 and ΔCBF were weakly correlated for the left (ρ 0.31, P = 0.4), and moderately correlated for the right (ρ 0.69, P = 0.03) hemisphere. The Bland-Altman plot suggested underestimation of ΔCBF by NIRS. Divergent associations of pH, pCO2 and arterial oxygen content with rSO2 were found compared to corresponding associations with CBF. In conclusion, NIRS could be a proxy to PET to detect intradialytic CBF changes, although NIRS and PET capture different physiological parameters of the brain.
The development of biocompatible membranes, aiming to limit the inflammatory response, oxidative stress, and coagulability during hemodialysis, has been an important step in reducing dialysis-related ...adverse outcomes. This includes a reduction in the risk of clotting of the extracorporeal circuit, thus enabling hemodialysis with a reduced dose or even without systemic anticoagulant drugs in patients with an increased bleeding risk. In this article, we summarize the in vitro research and clinical evidence on the antithrombotic properties of vitamin E- and heparin-coated membranes.
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