X-linked Alport syndrome presenting in mother and son with the same unique histopathological features.

Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4 and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman's capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman's capsule is more vulnerable to missense mutations in COL4A5 than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.

Synthetic ACTH for Treatment of Glomerular Diseases: A Case Series.

RATIONALE: Synthetic adrenocorticotropic hormone (Tetracosactide) has been used in the treatment of refractory glomerular diseases. Literature surrounding the use of this medication is limited to small case series and there is conflicting data on the rate of adverse events associated with this medication. PRESENTING CONCERNS OF THE PATIENT: Glomerulonephritis not in remission after at least 6 months of treatment with conservative care. Stable doses of concurrent immunosuppression were permitted. DIAGNOSES: Membranous nephropathy, IgA nephropathy, minimal change disease, and focal and segmental glomerulosclerosis. INTERVENTION: Intramuscular synthetic adrenocorticotropic hormone (Tetracosactide, Synacthen Depot) with doses of either 1 mg weekly or 1 mg twice weekly. OUTCOMES: Five of 12 patients had at least a partial remission with Tetracosactide. Median time to response was 6 months for responders. Five of the 12 patients had adverse events documented, 2 of which led to treatment discontinuation. No patients with focal and segmental glomerulosclerosis responded to treatment. LESSONS LEARNED: Higher rate of adverse events than previously reported with synthetic adrenocorticotropic hormone and uncertain treatment efficacy.

JUSTIFICATION: L'hormone adrénocorticotrope synthétique (tétracosactide) a été utilisée pour le traitement des maladies glomérulaires réfractaires. La littérature portant sur l'utilisation de ce médicament est limitée à de petites séries de cas et les données sur le taux d'événements indésirables associés à ce médicament sont contradictoires. PRÉSENTATION DES CAS: Glomérulonéphrites qui ne sont pas en rémission après un minimum de six mois de traitement conservateur. Des doses stables de traitement immunosuppresseur concomitant étaient autorisées. DIAGNOSTICS: Néphropathie membraneuse, néphropathie à IgA, néphropathie à lésion glomérulaire minime, hyalinose segmentaire et focale. INTERVENTIONS: Des doses soit de 1 mg par semaine soit de 1 mg deux fois par semaine d'hormone adrénocorticotrope synthétique (Tetracosactide, Synacthen Depot) administrées par voie intramusculaire. RÉSULTATS: Cinq patients sur douze ont connu au moins une rémission partielle avec le tétracosactide. Le délai de réponse médian était de six mois pour les patients qui répondaient au traitement. Cinq des douze patients ont eu des réactions indésirables documentées, dont deux ont entraîné l'arrêt du traitement. Aucun des patients présentant une hyalinose segmentaire et focale n'a répondu au traitement. ENSEIGNEMENTS TIRÉS: Un taux de réactions indésirables plus élevé que celui rapporté précédemment avec l'hormone adrénocorticotrope synthétique et une efficacité incertaine du traitement.

Three Weeks of Team-Based Leaning Do Not Overload Undergraduate Students.

CONTEXT: Team-based learning (TBL) is a flipped-classroom approach requiring students to study before class. Fully flipped curricula usually have fewer in-class hours. However, for practical reasons, several programs implement a few weeks of TBL without adjusting the semester timetable. Students fear that they will be overloaded by the individual and collaborative study hours needed to prepare for TBL. METHODS: We implemented three consecutive weeks of TBL in a 15-week lecture-based course on the renal system. In-class time and assessments were unchanged for all courses. Four hundred fifty-nine first-year undergraduate medical students (229 in 2018; 230 in 2019) were invited to complete weekly logs of their individual and collaborative study hours during lectures and TBL, along with questionnaires on cognitive load and perception of the course. Our program changed from A to E grading in 2018 to pass-fail grading in 2019. RESULTS: Participants (n = 324) spent a similar number of hours studying for TBL vs. lectures with a mean of 3.1 h/week. Collaborative study was minimal outside class (median 0.1 h/week). Results remained similar with pass-fail grading. If in-class time were reduced, 18% of participants said they would have used freed-up time to study for TBL. Studying for TBL generated similar extraneous cognitive load and lower intrinsic load compared to studying for lectures; students were less stressed, and maintained high levels of motivation and self-perceived learning. CONCLUSIONS: Three weeks of lectures were replaced by TBL without reducing in-class time. Students did not report overload in study hours or in cognitive load. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01314-x.

Health literacy level in a various nephrology population from Québec: predialysis clinic, in-centre hemodialysis and home dialysis; a transversal monocentric observational study.

BACKGROUND: Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. It is especially important in nephrology due to the complexity of chronic kidney disease (CKD). The present study sought to define health literacy levels in patients followed in predialysis clinic, in-center dialysis (ICHD), peritoneal dialysis (PD) and home hemodialysis (HHD). METHODS: This transversal monocentric observational study analysed 363 patients between October 2016 and April 2017. The Brief Health Literacy Screen (BHLS) and the Health Literacy Questionnaire (HLQ) were used to measure health literacy. Multivariate linear regressions were used to compare the mean scores on the BHLS and HLQ, across the four groups. RESULTS: Patients on PD had a significantly higher BHLS'score than patients on ICHD (p = 0.04). HLQ's scores differed across the groups: patients on HHD (p = 0.01) and PD (p = 0.002) were more likely to feel understood by their healthcare providers. Compared to ICHD, patients on HHD were more likely to have sufficient information to manage their health (p = 0.02), and patients in the predialysis clinic were more likely to report high abilities for health information appraisal (p < 0.001). CONCLUSION: In a monocentric study, there is a significant proportion of CKD patients, especially in predialysis clinic and in-centre hemodialysis, with limited health literacy. Patients on home dialysis (HHD and PD) had a higher level of health literacy compared to the other groups.

The use of vascular access audit and infections in home hemodialysis.

Vascular access-related infection is an important adverse event in home hemodialysis (HHD). We hypothesize that errors in self-cannulation or manipulation of dialysis vascular access are associated with increased incidence of access-related infection. We conducted a retrospective cohort study of all prevalent HHD patients at the University Health Network. All vascular access-related infections were recorded from 2006 to 2013. Errors in dialysis access were ascertained by nurse-administered vascular access checklist. Ninety-two patients had completed at least one vascular access audit. Median HHD vintage was 2.3 (0.9-5.0) years in patients with appropriate vascular access technique and 5.8 (1.5-9.4) years in patients with erroneous vascular access technique. The overall rate of infection between patients with and without appropriate vascular access technique was similar (0.27 and 0.28 infections per year, P = 0.166). Among patients who were identified with errors in dialysis access manipulation, patients with five or more errors were associated with higher rate of access-related infection (mean of 0.47 vs. 0.16 infection per patient-year, P < 0.001). The use of vascular access audit is a feasible strategy, which can identify errors in vascular access technique. Patients with a longer median HHD vintage are associated with higher risk of inappropriate vascular access technique. Patients with multiple errors in vascular access technique are associated with a higher risk of dialysis access-related infection. Prospective evaluation of the impact of vascular access audit on adverse vascular access events is warranted.

Effectiveness of Haemodiafiltration with Heat Sterilized High-Flux Polyphenylene HF Dialyzer in Reducing Free Light Chains in Patients with Myeloma Cast Nephropathy.

INTRODUCTION: In cases of myeloma cast nephropathy in need of haemodialysis (HD), reduction of free light chains using HD with High-Cut-Off filters (HCO-HD), in combination with chemotherapy, may be associated with better renal recovery. The aim of the present study is to evaluate the effectiveness of haemodiafiltration (HDF) in reducing free light chain levels using a less expensive heat sterilized high-flux polyphenylene HF dialyzer (HF-HDF). METHODS: In a single-centre prospective cohort study, 327 dialysis sessions were performed using a 2.2 m2 heat sterilized high-flux polyphenylene HF dialyzer (Phylther HF22SD), a small (1.1m2) or large (2.1 m2) high-cut-off (HCO) dialyzer (HCOS and HCOL) in a cohort of 16 patients presenting with dialysis-dependent acute cast nephropathy and elevated free light chains (10 kappa, 6 lambda). The outcomes of the study were the mean reduction ratio (RR) of kappa and lambda, the proportion of treatments with an RR of at least 0.65, albumin loss and the description of patient outcomes. Statistical analysis was performed using linear and logistic regression through generalized estimating equation analysis so as to take into account repeated observation within subjects and adjust for session duration. RESULTS: There were no significant differences in the estimated marginal mean of kappa RR, which were respectively 0.67, 0.69 and 0.70 with HCOL-HD, HCOS-HDF and HF-HDF (P = 0.950). The estimated marginal mean of the proportions of treatments with a kappa RR ≥0.65 were 68%, 63% and 71% with HCOL-HD, HCOS-HDF and HF-HDF, respectively (P = 0.913). The estimated marginal mean of lambda RR were higher with HCOL-HDF (0.78), compared to HCOL-HD and HF-HDF (0.62, and 0.61 respectively). The estimated marginal mean proportion of treatments with a lambda RR ≥0.65 were higher with HCOL-HDF (81%), compared to 57% in HF-HDF (P = 0.042). The median albumin loss were 7, 21 and 63 g/session with HF-HDF, HCOL-HD and HCOL-HDF respectively (P = 0.044). Among survivors, 9 out of 10 episodes of acute kidney injuries became dialysis-independent following a median time of renal replacement therapy of 40 days (range 7-181). CONCLUSION: Therefore, in patients with acute dialysis-dependent myeloma cast nephropathy, in addition to chemotherapy, HDF with a heat sterilized high-flux polyphenylene HF dialyzer could offer an alternative to HCO dialysis for extracorporeal kappa reduction with lower albumin loss.

Distal leg muscle function in patients with COPD.

Quadriceps muscle weakness and increased fatigability are well described in patients with chronic obstructive pulmonary disease (COPD). Whether these functional alterations also exist in distal leg muscles in patients with COPD is uncertain. Fifteen patients with COPD and 15 aged-matched healthy controls performed a 12-minute standardized treadmill exercise during which a fixed total expense of 40 Kcal was reached. The strength of i) dorsiflexors, ii) plantar flexors and iii) quadriceps was assessed at rest and after exercise using maximal voluntary contraction (MVC) and potentiated twitch force (Twpot). Resting MVC and Twpot were significantly lower in patients with COPD when compared with controls respectively for i) dorsiflexors (24.9 ± 8.4 vs. 31.2 ± 8.5 Nm, p < 0.05 and 4.3 ± 1.3 vs. 5.7 ± 1.8 Nm, p < 0.05), ii) plantar flexors (49.5 ± 11.8 vs. 62.1 ± 19.6 Nm, p < 0.05 and 10.8 ± 3.5 vs. 13.4 ± 2.7 Nm, p < 0.05), and iii) quadriceps muscles. There was a greater force loss in the distal leg muscles 15 minutes post-exercise in patients with COPD, while the strength of the quadriceps muscle remained stable in both groups. Patients with COPD had weaker dorsiflexor and plantar flexor muscles when compared to age-matched healthy controls. In addition, when exposed to the same absolute walking task, the fatigability of the distal leg muscles was higher in patients with COPD.

Gemella sanguinis endocarditis with c-ANCA/anti-PR-3-associated immune complex necrotizing glomerulonephritis with a 'full-house' pattern on immunofluorescence microscopy.

A 67-year-old man was evaluated for haematuria, with a rising creatinine level from 88 to 906 µmol/L and positive c-anti-neutrophil cytoplasm antibody (ANCA)/anti-proteinase 3 (anti-PR3). A kidney biopsy revealed necrotizing glomerulonephritis with a 'full-house' pattern on immunofluorescence microscopy. Echocardiography and blood cultures growing Gemella sanguinis diagnosed endocarditis. Dialysis was required for a month. Three months later, following valve replacement, glucocorticoids and 2 months of antibiotic therapy, the creatinine level decreased to 62 µmol/L and c-ANCA/anti-PR3 disappeared. This first case of c-ANCA/anti-PR3 positive glomerulonephritis with a 'full-house' immunofluorescence pattern due to bacterial endocarditis underlines the importance of ruling out infection with ANCA positivity or kidney biopsy suggestive of lupus nephritis.

Impact of donor age on long-term outcomes after delayed graft function: 10-year follow-up.

Delayed graft function (DGF) has a negative impact on graft survival in donation after brain death (DBD) but not for donation after cardiac death (DCD) kidneys. However, older donor age is associated with graft loss in DCD transplants. We sought to examine the interaction between donor age and DGF in DBD kidneys. This is a single-center, retrospective review of 657 consecutive DBD recipients transplanted between 1990 and 2005. We stratified the cohort by decades of donor age and studied the association between DGF and graft failure using Cox models. The risk of graft loss associated with DGF was not significantly increased for donor age below 60 years (adjusted hazard ratio [aHR] 1.12, 1.51, and 0.90, respectively, for age <40, 41-50 and 51-60 years) but significantly increased after 60 years (aHR 2.67; P = 0.019). Analysis of death-censored graft failure yielded similar results for donor age below 60 years and showed a substantially increased risk with donors above 60 years (aHR 6.98, P = 0.002). This analysis reveals an unexpectedly high impact of older donor age on the association between DGF and renal transplant outcomes. Further research is needed to determine the best use of kidneys from donors above 60 years old, where DGF is expected.