Sebastian Mussnig

Intradialytic hypotension (IDH) is a pervasive complication of hemodialysis, yet the clinical scenarios in which IDH occurs vary widely. To guide treatment standards, we describe five cases corresponding to typical IDH phenotypes: (i) acute intradialytic allergic event, with abrupt early hypotension reproducible with specific dialyzers; (ii) acute unexpected IDH due to autonomic imbalance (here, postprandial), with disproportionate symptoms despite modest blood pressure drops; (iii) chronic IDH due to hypovolemia from an overly ambitious target weight; (iv) chronic IDH with ultrafiltration-refill mismatch, where blood volume falls despite fluid overload; and (v) chronic hypotension due to limited cardiac reserve. In the acute setting (i-ii), immediate rescue—interruption of ultrafiltration and/or the dialysis session, Trendelenburg positioning, and isotonic fluid bolus—should be combined with rapid bedside phenotyping to identify allergic, autonomic, hypovolemic or cardiac triggers. Material hypersensitivity must be recognized, as rechallenge can be harmful, but is avoidable by dialyzer substitution. In the chronic setting (iii-v), prevention centers on reduced ultrafiltration stress: lower ultrafiltration rates with longer or more frequent sessions, and objective reassessment of target weight. The chronic phenotypes are often clinically indistinguishable yet require different corrections—a higher target weight in hypovolemia, gentler fluid removal that supports refilling in refill mismatch, and acceptance of some fluid overload with limited cardiac reserve—making objective volume assessment the decisive first step. The unifying concern is organ hypoperfusion, not blood pressure. Future trials should enroll phenotype-defined rather than heterogeneous ‘IDH-prone’ populations and use hard outcomes, end-organ ischemia and patient-reported outcomes.

Intradialytic hypotension (IDH) is a frequent complication of hemodialysis that may occur with symptoms and often requires interventions to restore hemodynamic stability and end-organ perfusion. In the absence of large trials with IDH as the primary endpoint, guidelines recommending specific management protocols are not available, but hemodynamic instability is a daily clinical reality, nevertheless. First, we suggest defining and monitoring IDH, by adopting a uniform IDH definition such as the Nadir90 criteria and document symptoms, and regularly measuring intradialytic as well as ambulatory blood pressure. Next, we give recommendations on how to treat IDH, by developing a standard operating procedure for acute events, and increasing dialysate sodium, and decreasing ultrafiltration rates and dialysate temperature. Finally, the majority of our tips are dedicated to preventing IDH, by regularly assessing fluid status, reviewing antihypertensive drugs, considering more frequent, longer or nocturnal dialysis, potentially considering hemodiafiltration, avoiding food and considering exercise, and trying automatic feedback algorithms. No single measure consistently prevents IDH, and each tip should be viewed as one lever among many. In practice, IDH is best managed by a layered, individualized approach that combines rigorous documentation, structured follow-up and a willingness to revisit the prescription each time hemodynamic instability recurs.

The start of hemodialysis is a particularly vulnerable phase in a patient’s journey through various stages of kidney disease: Early mortality is high, functional decline is common, and many patients feel poorly informed and unprepared for what dialysis entails. Decisions made during this phase shape long-term trajectories. Here, we aim at providing “suggestions for colleagues” rather than guideline-like recommendations. In our six tips regarding dialysis consent, transplant candidacy, pill check, vaccination, exercise, and nutrition, we cover the direct patient–doctor axis. In our four tips on volume management, modality, anticoagulation, and incremental hemodialysis, we provide advice that may benefit patients through the prescription itself. Our choice of items is incomplete, as important aspects like vascular access, anemia management, mineral bone disorder, patient-reported symptoms, and dialysate composition are missing. Altogether, we hope that our contribution can emphasize, that hemodialysis may be viewed as the cradle rather than the dead end of nephrology, and enthusiasm for the accomplishments of hemodialysis over the years can ultimately outperform frustration over the burden it imposes on patients. Today’s many options to modify hemodialysis for the better represent professional challenges, but these can ultimately be used, right from the start, such as to build the perfect, individualized patient package that should be hemodialysis treatment today.

Background: Ambulatory blood pressure (BP) and pulse wave characteristics (PWCs) are stronger predictors of mortality than conventional pre-/post-dialytic BP in hemodialysis. While BP is recommended to be managed primarily by reducing fluid overload (FO), associations of FO with interdialytic BP/PWCs remain unknown. Methods: Bioimpedance-derived FO and interdialytic 44-h BP/PWCs were analyzed at baseline and follow-up of a quality improvement project involving targeted fluid management. Trended cosinor linear mixed-effects models assessed intra-patient associations of post-dialysis FO with interdialytic BP/PWCs. Results: We analyzed 120 visits (77/43 at baseline/follow-up) from 80 patients (70% male; mean age 68 ± 14 years; median dialysis vintage 38 [18–64] months). Post-dialysis FO decreased in baseline hypervolemic patients from 2.7 ± 1.3 L to 0.9 ± 1.7 L. Every 1 L increase in post-dialysis FO at the patient level was associated with increased peripheral BP (systolic: 4.54 mmHg, P < 0.001; diastolic: 2.55 mmHg, P < 0.001), peripheral resistance (0.03 s*mmHg/mL, P = 0.011), augmentation index (1.38%, P = 0.007), wave amplitudes (forward: 0.56 mmHg, P = 0.025; backward: 0.61 mmHg, P = 0.027), reservoir pressure peak (3.83 mmHg, P < 0.001), and pulse wave velocity (0.12 m/s, P = 0.007). Higher FO was associated with decreased interdialytic slopes of all BPs, peripheral resistance, backward wave amplitude, reservoir peak pressure, and pulse wave velocity. FO interacted with circadian rhythms of stroke volume, peripheral resistance, forward wave amplitude, and excess pressure peak. Conclusions: We showed that FO in hemodialysis is associated with increased interdialytic BP and PWCs on a patient level, and that FO blunts interdialytic BP/PWC trends. We further establish that physiological BP/PWC patterns may be associated with euvolemic fluid status, hence making the case for tailoring target weight using bioimpedance spectroscopy.

Introduction: Arterial pulse wave-derived features (PWFs) reflect hemodynamic changes during hemodialysis, and while their use is not currently recommended by clinical practice guidelines, many PWFs are associated with patient outcomes beyond classical blood pressure measurements. Pre-dialysis fluid overload (FO), intradialytic relative blood volume (RBV), and cumulative ultrafiltration volume (cUFV) may influence PWFs, but these relationships remain incompletely characterized. We aimed to explore associations between FO, RBV, cUFV, and PWFs during hemodialysis. Methods: We analyzed 79 hemodialysis sessions in 24 patients over 5 weeks. Each session included pre-dialysis bioimpedance spectroscopy, cuff-based pulse wave measurements every 15 min, and continuous RBV/cUFV monitoring. Associations between RBV or cUFV and 28 PWFs (including blood pressure measures, parameters of cardiac function, and various arterial wave features derived from pulse wave analysis) were assessed using confounder-adjusted generalized estimating equations. Repeated-measures correlation analysis evaluated within-patient associations between pre-dialysis FO and both initial PWF levels (median from the first 45 min) and their intradialytic changes (late minus early 45-min median). Results: We analyzed 817 pulse wave measurements from 24 patients (21 men; median age 66 years). Overall, RBV was associated with 18/28 PWFs (64%) and cUFV with 10/28 (36%), with distinct patterns: independently of each other, RBV was associated mainly with stroke volume, cardiac output, heart rate, systolic and reflected intensity peaks, and excess pressure; cUFV mainly with diastolic blood pressure, peripheral resistance, reservoir pressure, and the ratio of forward intensity peaks. Significant early-to-late intradialytic changes in PWFs included a decrease in stroke volume, reflection coefficient, and cardiac output, as well as an increase in pulse pressure amplification and reflected intensity peak. Among initial PWF levels, only the excess pressure integral correlated with pre-dialysis FO; however, FO correlated positively with intradialytic changes in systolic and mean blood pressure, pulse wave velocity, and reservoir pressure, indicating attenuated decreases in these parameters when baseline fluid excess was higher. Conclusion: In the studied cohort, RBV and cUFV showed distinct association profiles with PWFs during hemodialysis. These relationships warrant consideration in studies assessing or intervening on PWFs in dialysis patients.

Background: Bioimpedance and absolute blood volume measurement are objective assessments of volume status. However, uncertainties remain in their application at extreme body habitus. We aimed to compare blood volume and bioimpedance-based volume status at extreme body habitus and explore normalisation of blood volume in this context to support incorporation of these tools into fluid management decisions. Methods: We defined two common extreme volume-status phenotypes in haemodialysis: obese and bioimpedance-dry (n = 29) and lean and bioimpedance-wet (n = 29). Control subjects were haemodialysis patients who were haemodynamically stable with normal volume status (n = 20). We compared post-dialysis blood volume at clinical “target weight”, measured by dialysate dilution, in the obese/dry and lean/wet groups with controls. We explored normalisation of blood volume (n = 98) by body mass, lean tissue mass and an anthropometric-based estimate of blood volume determined by Lemmens' formula. Results: Post-dialysis blood volume normalized for body mass (specific blood volume) was lower in the obese/dry (57.9 mL/kg; P = 0.02) and higher in the lean/wet group (84.5 mL/kg; P = 0.001) than in controls (68.0 mL/kg). These differences were not present for lean tissue mass-normalised or Lemmens' formula-normalised blood volume. Normalising blood volume to body mass results in differences by sex and body mass, whereas normalising to Lemmens blood volume, which accounts for fat mass variation, does not. Conclusions: Setting target weights to achieve fixed reference bioimpedance or blood volume values may not be appropriate at extreme body habitus, reinforcing the need for individualised approaches. Normalising blood volume to body mass may exacerbate established measurement bias observed with bioimpedance.

Background: Fluid monitoring is critical for patients on maintenance hemodialysis. Bioimpedance enables estimation of fluid volumes from measures of electrical tissue properties. However, empirical equations are needed to approximate key variables, especially in wrist-to-ankle bioimpedance measurements, introducing potential errors. Summary: Here, we provide a technical overview of electrical impedance, derivation of fluid volumes from different bioimpedance methods and electrode setups, as well as sources of error including the assumption of constant resistivity, constant body temperature, and vendor-specific equations to derive fluid overload. We summarize the validity of bioimpedance methods in hemodialysis and conclude that irrespective of error sources reported above, segmental bioimpedance, where limbs and the trunk are measured separately, may be more accurate compared to the convenient wrist-to-ankle measurement. We argue that insufficient correction for variable body shape in wrist-to-ankle measurements jeopardizes this methodology, reporting here our analyses by means of theory and data simulation, where we found that conventional wrist-to-ankle bioimpedance underestimated extracellular fluid volume with increasing body fat percentage. The error could be reduced by using subject specific body shape correction based on high-resolution 3D models. Finally, we attempt to provide guidance for identifying and mitigating common issues of wrist-to-ankle bioimpedance. Key Messages: While more convenient than segmental measurements, wrist-to-ankle bioimpedance may underestimate fluid volumes in obesity when body shape is not properly accounted for. Novel techniques, including smartphone-based 3D scans of the body, could potentially facilitate individualizing body shape correction to improve fluid volume estimates.

Background: Post-acute sequelae of severe acute respiratory syndrome coronavirus 2-infection (PASC) is challenging to diagnose and treat, and its molecular pathophysiology remains unclear. Urinary peptidomics can provide valuable information on urine peptides that may enable improved and specified PASC diagnosis. Methods: Using standardized capillary electrophoresis-MS, we examined the urinary peptidomes of 50 patients with PASC 10 months after COVID-19 and 50 controls including healthy individuals (n = 42) and patients with non-COVID-19-associated myalgic encephalomyelitis/chronic fatigue syndrome (n = 8). Based on peptide abundance differences between cases and controls, we developed a diagnostic model using a support vector machine. Results: The abundance of 195 urine peptides among PASC patients significantly differed from that in controls, with a predominant abundance of collagen alpha chains. This molecular signature (PASC195), effectively distinguished PASC cases from controls in the training set [AUC of 0.949 (95% CI 0.900–0.998; p < 0.0001)] and independent validation set [AUC of 0.962 (95% CI 0.897–1.00); p < 0.0001)]. In silico assessment suggested exercise, GLP1-RA and MRA as potentially efficacious interventions. Conclusions: We present a novel and non-invasive diagnostic model for PASC. Reflecting its molecular pathophysiology, PASC195 has the potential to advance diagnostics and inform therapeutic interventions. Statement of significance of the study: Despite the recent emergence of omics-derived candidates for post-acute sequelae of SARS-CoV-2 infection (PASC), the pending validation of proposed markers and lack of consensus result in the continuous reliance on symptom-based criteria, being subject to diagnostic uncertainties and potential recall bias. Building upon prior findings of renal involvement in acute COVID-19 pathophysiology and PASC-associated alterations, we hypothesized that the use of urinary peptides for PASC-specific biomarker discovery, unlike conventional specimens that have been utilized thus far, may offer complementary information on putative disease mechanisms. In the present study, 195 significantly expressed peptides were used to form a classifier termed PASC195, which effectively discriminated PASC from non-PASC (p < 0.0001), including healthy individuals and non-COVID-19 associated myalgic encephalomyelitis/chronic fatigue syndrome, in both the derivation (n = 60) and an independent validation set (n = 40). Shift in collagen regulation was associated with PASC, as the majority of PASC195 peptides were derived from collagen alpha chains. Ongoing inflammatory responses, hemostatic imbalances, and endothelial damage were inferred from cross-sectional variations in endogenous peptide excretion.