Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied \u201ccountry-specific\u201d factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a \u201cone-size-fits-all\u201d approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions

Sex Disparity in Cause-Specific and All-Cause Mortality Among Incident Dialysis Patients

Rationale & Objective: Early mortality rates of female patients receiving dialysis have been, at times, observed to be higher than rates among male patients. The differences in cause-specific mortality between male and female incident dialysis patients with kidney failure are not well understood and were the focus of this study. Study Design: Retrospective cohort study. Setting & Participants: Incident patients who had initiated dialysis in Australia and New Zealand in 1998-2018. Exposure: Sex. Outcomes: Cause-specific and all-cause mortality while receiving dialysis, censored for kidney transplant. Analytical Approach: Adjusted cause-specific proportional hazards models, focusing on the first 5 years following initiation of dialysis. Results: Among 53,414 patients (20,876 [39%] female) followed for a median period of 2.8 (IQR, 1.3-5.2) years, 27,137 (51%) died, with the predominant cause of death attributed to cardiovascular disease (18%), followed by dialysis withdrawal (16%). Compared with male patients, female patients were more likely to die in the first 5 years after dialysis initiation (adjusted hazard ratio [AHR], 1.08 [95% CI, 1.05-1.11]). Even though female patients experienced a lower risk of cardiovascular disease–related mortality (AHR, 0.93 [95% CI, 0.89-0.98]) than male patients, they experienced a greater risk of infectionrelated (AHR, 1.20 [95% CI, 1.10-1.32]) and dialysis withdrawal–related (AHR, 1.19 [95% CI, 1.13-1.26]) mortality. Limitations: Possibility of residual and unmeasured confounders. Conclusions: Compared with male patients, female patients had a higher risk of all-cause mortality in the first 5 years after dialysis initiation, a difference driven by higher rates of mortality from infections and dialysis withdrawals. These findings may inform the study of sex differences in mortality in other geographic settings.Wai H. Lim, Jenny H.C. Chen, Kimberley Minas, David W. Johnson, Maleeka Ladhani, Esther Ooi, Neil Boudville, Carmel Hawley, Andrea K. Viecelli, Matthew Roberts, Kate Wyburn, Rachael Walker, Monique Borlace, Helen Pilmore, Christopher E. Davies, Charmaine E. Lok, Armando Teixeira-Pinto, and Germaine Won

Novel phosphopantothenoylcysteine synthetase (<em>PPCS</em>) mutations with prominent neuromuscular features: Expanding the phenotypical spectrum of <em>PPCS</em>-related disorders.

Biallelic pathogenic variants in phosphopantothenoylcysteine synthetase, PPCS, are a rare cause of a severe early-onset dilated cardiomyopathy with high morbidity and mortality. To date, only five individuals with PPCS-mutations have been reported. Here, we report a female infant who presented in the neonatal period with hypotonia, a necrotizing myopathy with intermittent rhabdomyolysis and other extracardiac manifestations before developing a progressive and ultimately fatal dilated cardiomyopathy. Gene agnostic trio genome sequencing revealed two rare variants in the PPCS [MIM: 609853] in trans, a previously reported pathogenic c.320_334del p. (Pro107_Ala111del) variant, and a c.613-3C&gt;G intronic variant of uncertain significance. Functional studies confirmed the likely pathogenicity of this variant. Our case provides clinical and histopathological evidence for an associated neuromuscular phenotype not previously recognized and expands the evolving phenotypic spectrum of PPCS-related disorders. We also performed a literature search of all previously published cases and summarize the common features

Feline heartworm disease: a clinical review

Feline heartworm disease is caused by the filarial nematode Dirofilaria immitis, and is transmitted by mosquitoes in heartworm-endemic areas worldwide. While dogs are the definitive hosts for this parasite, cats can also be infected, and the overall prevalence in cats is between 5% and 10% of that in dogs in any given area. The spectrum of feline presentations varies from asymptomatic infections to chronic respiratory signs, sometimes accompanied by chronic vomiting to acute death with no premonitory signs. Ante-mortem diagnosis can be challenging and relies on a combination of tests, including antigen and antibody serology, thoracic radiography and echocardiography. As treatment with heartworm adulticidal drugs can be life-threatening and heartworm infection in cats is often self-limiting, infected cats are frequently managed with supportive treatment (corticosteroids, bronchodilators, and anti-emetics). Surgical removal of filariae using extraction devices may be considered in some acute cases where immediate curative treatment is necessary, but filarial breakage during the procedure may result in an acute fatal shock-like reaction. Necropsy findings are mainly pulmonary and include muscular hypertrophy of the pulmonary arteries and arterioles on histopathology. A number of safe and effective macrocytic lactone drugs are available for prophylaxis in cats. These drugs can kill a range of larval and adult life-cycle stage heartworms, which may be advantageous in cases of owner compliance failure or when heartworm infection status is undetermined at the time prophylaxis is commenced. An index of suspicion for feline heartworm disease is warranted in unprotected cats with respiratory signs, and perhaps chronic vomiting, in areas where canine heartworm disease is endemic. Many cats, once diagnosed and with appropriate supportive care and monitoring, will resolve their infection and be free of clinical signs