Exaggerated blood pressure response to dynamic exercise despite chronic refractory hypotension : results of a human case study

BACKGROUND: Chronic refractory hypotension is a rare but significant mortality risk in renal failure patients. Such aberrant physiology usually deems patient unfit for renal transplant surgery. Exercise stimulates the mechano-chemoreceptors in the skeletal muscle thereby modulating the sympathetic effects on blood pressure regulation. The haemodynamic response to dynamic exercise in such patients has not been previously investigated. We present a case with severe chronic hypotension who underwent exercise testing before and after renal transplantation, with marked differences in blood pressure response to exercise. CASE PRESENTATION: A 40-year old haemodialysis-dependent patient with a 2 year history of refractory hypotension (≤80/50 mmHg) was referred for living donor renal transplantation at our tertiary centre. Each dialysis session was often less than 2 h and 30 min due to symptomatic hypotension. As part of the cardiovascular assessment, she underwent haemodynamic evaluation with cardiopulmonary exercise testing. Blood pressure normalized during unloaded pedalling but was exaggerated at maximal workload whereby it rose from 82/50 mmHg to a peak of 201/120 mmHg. Transthoracic echocardiography, tonometric measure of central vascular compliance and myocardial perfusion scan were normal. She subsequently underwent an antibody-incompatible renal transplantation and was vasopressor reliant for 14 days during the post-operative period. Eight weeks following transplant, resting blood pressure was normal and a physiological exercise-haemodynamic response was observed during a repeat cardiopulmonary exercise testing. CONCLUSION: This case highlights the potential therapeutic role of unloaded leg cycling exercise during dialysis session to correct chronic hypotension, allowing patients to have greater tolerance to fluid shift. It also adds to existing evidence that sympathetic dysfunction is reversible with renal transplant. Furthermore chronic hypotension with preserved exercise-haemodynamic response and cardiovascular reserve should not preclude these patients from renal transplant surgery

Effect of dietary potassium restriction on serum potassium, disease progression, and mortality in chronic kidney disease : a systematic review and meta-analysis

Low-potassium diets are recommended to reduce serum potassium (Sk) and prevent complications of chronic kidney disease (CKD), but evidence underpinning this recommendation has not been systematically reviewed and synthesized. We conducted a systematic review comparing change in Sk, CKD progression, and mortality between those on a low-potassium versus unrestricted potassium diet. We searched Medline, AMED, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, and Clinicaltrials.org from inception to 3 April 2018. We included randomized and observational studies that compared these outcomes in adults with CKD who ate a restricted versus unrestricted amount of dietary potassium. We pooled mean change in Sk and adjusted hazard ratios of disease progression and mortality using random-effects meta-analyses. We identified 5,563 articles, of which seven studies (3,489 participants) met our inclusion criteria. We found very low-quality evidence that restricted (1,295 mg/d) versus unrestricted (1,570 mg/d) dietary potassium lowered Sk by -0.22 mEq/L (95% confidence interval [CI]: -0.33, -0.10; I  = 0%). Lower (1,725 mg/d) versus higher (4,558 mg/d) dietary potassium was not significantly associated with disease progression (hazard ratio [HR]: 1.14; 95% CI: 0.77, 1.70; I  = 57%). Lower (1,670 mg/d), compared with higher (4,414 mg/d) dietary potassium intake was associated with a 40% reduction in mortality hazard (HR: 0.60; 95% CI: 0.40, 0.89; I  = 56%). Very-low-quality evidence supports consensus that dietary potassium restriction reduces Sk in normokalemia and is associated with a reduced risk of death in those with CKD. High-quality randomized controlled trials are needed. [Abstract copyright: Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Behaviour of non-donor specific antibodies during rapid re-synthesis of donor specific HLA antibodies after antibody incompatible renal transplantation

Background: HLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation. Methods: 55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified. Results: Despite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00). Conclusion: In spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection

Dynamic behaviour of donor specific antibodies in the early period following HLA incompatible kidney transplantation

In HLA-incompatible kidney transplantation, monitoring donor-specific antibodies (DSA) plays a crucial role in providing appropriate treatment and increases kidney survival times. This work aimed to determine if early post-transplant DSA dynamics inform graft outcome over and above other predictive factors. Eighty-eight cases were classified by unsupervised machine learning into five distinct DSA response groups: no response, fast modulation, slow modulation, rise to sustained and sustained. Fast modulation dynamics gave an 80% rate for early acute rejection, whereas the sustained group was associated with the lowest rejection rates (19%). In complete contrast, the five-year graft failure was lowest in the modulation groups (4–7%) and highest in the sustained groups (25–31%). Multivariable analysis showed that a higher pre-treatment DSA level, male gender and absence of early acute rejection were strongly associated with a sustained DSA response. The modulation group had excellent five-year outcomes despite higher rates of early rejection episodes. This work further develops an understanding of post-transplant DSA dynamics and their influence on graft survival following HLA-incompatible kidney transplantation

C3d‐positive donor‐specific antibodies have a role in pretransplant risk stratification of cross‐match‐positive HLA‐incompatible renal transplantation : United Kingdom multicentre study

Anti‐HLA‐antibody characteristics aid to risk‐stratify patients and improve long‐term renal graft outcomes. Complement activation by donor‐specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross‐match‐positive). We explored the role of C3d‐positive DSAs in sub‐stratification of cross‐match‐positive cases and relate to the graft outcomes. We investigated 139 cross‐match‐positive living‐donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post‐transplant. C3d‐positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post‐transplant. Median follow‐up of patients was 48 months (IQR 20.47–77.57). In the multivariable analysis, pretreatment C3d‐positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37–7.86). The relative risk of death‐censored five‐year graft failure was 2.83 (95% CI 1.56–5.13). Patients with both pretreatment and Day 14 C3d‐positive DSAs had the worst five‐year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d‐negative DSA patients with the relative risk of death‐censored five‐year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub‐stratify the risk of poor graft outcome in cross‐match‐positive living‐donor renal transplantation

HLA antibody incompatible renal transplantation : long-term outcomes similar to deceased donor transplantation

Background. HLA incompatible renal transplantation still remains one of best therapeutic options for a subgroup of patients who are highly sensitized and difficult to match but not much is known about its long-term graft and patient survival. Methods. One hundred thirty-four HLA incompatible renal transplantation patients from 2003 to 2018 with a median follow of 6.93 y were analyzed retrospectively to estimate patient and graft survivals. Outcomes were compared with groups defined by baseline crossmatch status and the type and timings of rejection episodes. Results. The overall patient survival was 95%, 90%, and 81%; and graft survival was 95%, 85%, and 70% at 1, 5, and 10 y, respectively. This was similar to the first-time deceased donor transplant cohort. The graft survival for pretreatment cytotoxic-dependent crossmatch (CDC) positive crossmatch group was significantly low at 83%, 64%, and 40% at 1, 5, and 10 y, respectively, compared with other groups (Bead/CDC, P = 0.007; CDC/Flow, P = 0.001; and microbead assay/flow cytometry crossmatch, P = 0.837), although those with a low CDC titer (<1 in 2) have comparable outcomes to the CDC negative group. Female patients in general fared worse in both patient and graft survival outcomes in each of the 3 groups based on pretreatment crossmatch, although this did not reach statistical significance. Antibody-mediated rejection was the most frequent type of rejection with significant decline in graft survival by 10 y when compared with no rejection (P < 0.001). Rejection that occurred or continued to occur after the first 2 wk of transplantation caused a significant reduction in graft survivals (P < 0.001), whereas good outcomes were seen in those with a single early rejection episode. Conclusions. One-, 5-, and 10-y HLA incompatible graft and patient survival is comparable to deceased donor transplantation and can be further improved by excluding high-CDC titer cases. Antibody-positive female patients show worse long-term survival. Resolution of early rejection is associated with good long-term graft survival

Evaluation of periodontal status and detection of Dialister pneumosintes in cerebral palsy individuals: A Case–Control study

Background: The worldwide prevalence of cerebral palsy among live births is estimated to be between 1.9 and 3.6/1000. The presence of periodontal disease in cerebral palsy children typically is due to bacterial plaque accumulation caused by their inability to correctly clean their own teeth, difficulties in chewing and swallowing food, and improper movements of masticatory muscles and tongue muscles. Objectives: The objective of this study is to estimate the periodontal status in cerebral palsy individuals and evaluate the presence of Dialister pneumosintes. Materials and Methods: Thirty cerebral palsy children from the Spastics Society of Tamilnadu with signs of periodontitis were compared with the same number of age- and gender-matched controls for oral hygiene and periodontal parameters. Subgingival plaque samples were screened for the presence of respiratory pathogen D. pneumosintes by polymerase chain reaction (PCR). Results: A variation was noted between types of cerebral palsy individuals with a mean probing pocket depth value of 6 in spastic type, 4.86 in the ataxic, and 4.3 in the dyskinetic. Clinical attachment level varied from 6.71 in spastic to 5.43 in ataxic and 3.50 in dyskinetic. Oral hygiene index-simplified ranged from 2.764 in spastic to 2.25 in ataxic and 1.41 in dyskinetic. PCR results indicated 25% and 21.7% positivity for D. pneumosintes among cerebral palsy and control group, respectively. The odds ratio calculated to estimate the risk of periodontitis due to D. pneumosintes was 0.765. Conclusion: It was concluded that oral hygiene status and severity of periodontitis worsens as the rigidity and muscle tone limiting limb movement increases in cerebral palsy individuals

Synthesis of nanostructured titanium nitride films by PLD through reactive processing

High quality TiN films were synthesised from elemental metallic target using reactive and plasma assisted pulsed laser deposition (RPLD and PAPLD) techniques. In these processes, a high pure titanium target is ablated using a nanosecond pulsed Nd:YAG laser operating at 1064 nm wavelength at different nitrogen pressures. In RPLD process, the titanium plume reacts directly with the nitrogen gas at pressures less than 0.07 mbar to yield TiN films. In PAPLD process, additional nitrogen plasma was generated and confined by a DC coil positioned between target and substrate. Resultant films were characterised for phase, composition and morphology using glancing incidence X-ray diffraction, Auger Electron Spectroscopy (AES), Rutherford back-scattering and Atomic Force Microscope (AFM). Reactive pulsed laser deposition grown TiN films were found to contain traces of unreacted titanium. The crystallite size is estimated to be 15 and 50 nm respectively by using X-ray diffraction and AFM. Rutherford backscattering investigations helped the authors in arriving at the stoichiometry and AES analysis revealed the formation of TiN with low oxygen contamination

Reactive pulsed laser deposition of titanium nitride thin films: effect of reactive gas pressure on the structure, composition, and properties

Titanium nitride (TiN) thin films were deposited by reactive pulsed laser deposition (RPLD) technique. For the first time, the composition evaluated from proton elastic backscattering spectrometry, in a quantitative manner, revealed a dependence on the partial pressure of nitrogen from 1 to 10 Pa. Grazing incidence-XRD (GI-XRD) confirmed the formation of predominantly nanocrystalline TiN phase with a crystallite size of around 30 nm. The hardness showed maximum value of ~30 GPa when the composition is near stoichiometric and the friction coefficient was found to be as low as 0.3. In addition, a systematic optical response was observed as a function of deposition pressure from the surface of the TiN films using spectroscopic ellipsometry