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Introduction: QTc interval prolongation is increasingly frequent as chronic kidney disease (CKD) advances and predicts death in dialysis. However, predictors and mortality risk in predialysis CKD are understudied. FGF23 induces left ventricular hypertrophy (LVH) which is associated with QTc interval prolongation and death, suggesting a possible pathway from FGF23 to death that entails LVH and QTc prolongation. We looked for links between FGF23 and prolonged QTc intervals mediated by LVH and for deaths associated with QTc prolongation in a prospective observational cohort of patients with predialysis CKD., Methods: Participants underwent protocolized baseline and semiannual FGF23 testing, baseline and study end echocardiograms, and baseline and annual electrocardiograms over 3 years., Results: A total of 2,254 participants (34.1% female; mean age: 68.7 years; mean glomerular filtration: rate 41.4 mL/min/m2) enrolled in the study. Baseline LVH (left ventricular mass index >131 g/m2 [>100 g/m2 if female]) was present in 10.8% and prolonged QTc intervals (≥500 ms) in 1.5% of participants. One hundred thirty-eight (6.1%) participants died during the study. In generalized mixed-effects regression, each unit increase in the natural log of FGF23 - but not LVH - predicted an odds ratio of 1.76 (1.15, 2.70, p = 0.009) for prolonged QTc intervals independently of 15 other covariates. Mediation analysis showed that only 13% of FGF23's total effect on prolonged QTc intervals was mediated by LVH. Patients with prolonged QTc intervals had higher unadjusted (log rank p < 0.001) and adjusted (hazard ratio: 2.06 [1.08, 3.92, p = 0.028]) mortality rates than those with QTc intervals <500 ms., Discussion: QTc interval prolongation ≥500 ms was prospectively associated with FGF23 independently of LVH and with increased mortality risk in patients with predialysis CKD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease., Sources of Information: Peer-reviewed clinical trials and observational studies., Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist., Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture., Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Small randomized trials demonstrated that a lower compared with higher dialysate temperature reduced the average drop in intradialytic blood pressure. Some observational studies demonstrated that a lower compared with higher dialysate temperature was associated with a lower risk of all-cause mortality and cardiovascular mortality. There is now the need for a large randomized trial that compares the effect of a low vs high dialysate temperature on major cardiovascular outcomes., Objective: The purpose of this study is to test the effect of outpatient hemodialysis centers randomized to (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol for 4 years on cardiovascular-related death and hospitalizations., Design: The design of the study is a pragmatic, registry-based, open-label, cluster randomized controlled trial., Setting: Hemodialysis centers in Ontario, Canada, were randomized on February 1, 2017, for a trial start date of April 3, 2017, and end date of March 31, 2021., Participants: In total, 84 hemodialysis centers will care for approximately 15 500 patients and provide over 4 million dialysis sessions over a 4-year follow-up., Intervention: Hemodialysis centers were randomized (1:1) to provide (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol of 36.5°C. For the personalized protocol, nurses set the dialysate temperature between 0.5°C and 0.9°C below the patient's predialysis body temperature for each dialysis session, to a minimum dialysate temperature of 35.5°C., Primary Outcome: A composite of cardiovascular-related death or major cardiovascular-related hospitalization (a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) captured in Ontario health care administrative databases., Planned Primary Analysis: The primary analysis will follow an intent-to-treat approach. The hazard ratio of time-to-first event will be estimated from a Cox model. Within-center correlation will be considered using a robust sandwich estimator. Observation time will be censored on the trial end date or when patients die from a noncardiovascular event., Trial Registration: www.clinicaltrials.gov; identifier: NCT02628366., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Zager is the Medical Director for Dialysis Clinic Inc, which provided partial funding for Major Outcomes with Personalized Dialysate TEMPerature (MyTEMP). Dr Wald has received unrestricted research support from Baxter Healthcare. The remaining authors declare they have no other relevant interests., (© The Author(s) 2020.)

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Biomarkers that predict end-stage renal disease (ESRD) and/or mortality could usher in new therapeutics to halt this onslaught. While fibroblast growth factor (FGF)23 can predict both ESRD and mortality, it has not been studied in North American CKD patients of Asian ethnicity., Method: This is a prospective investigation about the role of FGF23 in 998 Canadian patients of Asian descent with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/m2 and followed up for 3 years., Results: The mean age of patients was 68.9 years and 68.3% were males. The mean (range) eGFR, and median FGF23 were 40.2 (11.0-59.0) mL/min and 154.1 (7.0-7,823.0) RU/mL, respectively. Over the 3 years, higher values of FGF23 levels at baseline were associated with higher risk of ESRD (hazard ratio [HR] for log[Fgf23] = 2.16 [95% CI 1.20-3.89]). Despite the short follow-up, 42 patients died due to cardiovascular diseases (38.8%), cancer (14.9%), and infections (12.7%). Log-FGF23 levels were independently associated with death, HR 1.94, 95% CI 1.24-3.03. Mortality risk increased in FGF23 subgroups from <100 to >400 RU/mL. In a time-changing covariate analysis, serial log-FGF23 levels over the 3 years predicted mortality with a HR of 2.66 (95% CI 1. 79-3.95)., Conclusion: In a Canadian Asian population with CKD, FGF23 levels obtained at 6-monthly intervals for 3 years predicted ESRD and mortality suggesting that it is also a risk marker in Asians., (© 2017 S. Karger AG, Basel.)

Introduction: We developed the Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST) to permit hemodialysis (HD) patients with central venous catheters (catheters) to shower without additional infection risk. Our primary objective was to determine the feasibility of conducting a parallel randomized controlled trial (RCT) to evaluate the impact of HIPPO-ST on catheter-related bacteremia (CRB) in adult HD patients., Methods: Adult HD patients using catheters were recruited from 11 HD units. Patients were randomized to receive HIPPO-ST or standard care and were followed up for 6 months. Only CRB-outcome assessors were blinded. For the study to be considered feasible, 4 of 5 feasibility outcomes, each with its own statistical threshold for success, must have been achieved., Results: A total of 68 patients were randomized (33 HIPPO-ST and 35 control) and were followed up to 6 months. Of 5 measures of feasibility, 4 were achieved: (1) accurate CRB rate documented (threshold: κ level >0.80); (2) 97.8% (279/285) of satellite HD patients with catheters were screened (threshold: >95%); (3) 88% (23/26) in the HIPPO-ST arm were successfully educated by 6 months (threshold: >80%); and (4) 0% (0/29) patients in the control arm were "contaminated," that is, using HIPPO-ST (threshold: <5%). However, only 44.2% (72/163) of eligible patients consented to participate (threshold: >80%). The rate of CRB was similarly low in HIPPO-ST and control groups (0.68 vs. 0.88/1000 catheter days)., Discussion: This HIPPO-ST pilot study demonstrated the feasibility of the larger HIPPO-ST study, especially given the high levels of education success with the HIPPO-ST arm and the low levels of contamination in the control arm.

Cognitively impaired patients often pull at their dialysis catheters when the catheters are tunneled over the anterior chest. To potentially circumvent this, a technique was developed that tunnels the catheter posteriorly, over the patient's shoulder. A total of 32 posteriorly tunneled catheters were placed in 12 patients. The mean catheter use interval was 164 days, with a total of 5,248 catheter use days. Indications for nonelective catheter removals were catheter dysfunction (n = 7; 23.3%), removal by the patient (n = 7; 23.3%), infection (n = 5; 16.7%), and inadvertent dislodgment (n = 1; 3.3%). Only six of the 12 patients were able to dislodge their catheters. The procedure described here reduced catheter manipulation and extended catheter viability in these patients., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted., Methods: More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay., Results: Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies., Conclusion: Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.

This survey was undertaken to determine the clinical spectrum and outcome of SLE in hospitalized African blacks in Durban, South Africa. We reviewed the hospital records of all patients with SLE who were seen during 1984 and 1990. Eighty-five patients were seen and their mean age at diagnosis was 33.3 years. The prevalence of the various diagnostic criteria was as follows: cutaneous, 68%; arthritis, 66%; renal, 65%; serositis, 29%; neuropsychiatric, 21%; haematological, 71%; immunological, 49%; anti-nuclear factor, 98%. Follow up data were not available in many patients but 25 (29%) are known to have died. The commonest causes of death were renal, infection, neurological and cardiac. This survey shows that SLE is being recognized more frequently in African Blacks and is associated with a high mortality.

Acute renal failure (ARF) has changed in its aetiology in developed Western countries. This study compares our experiences of the aetiology and incidence of ARF a decade after a previously recorded paper in the literature. The data of 226 patients with a diagnosis of ARF during a 3-year period from 1986 to 1988 was analysed. ARF in our study occurred at a younger age. Medical causes of ARF remain the dominant subgroup. There were female patients presenting with ARF associated with self-induced abortions. Toxins of a herbal variety and infections remain the commonest aetiological factors in the medical subgroup. Infections have replaced nephrotoxins as being the principal medical cause. There has been no major change in the incidence or aetiology of ARF over a decade. The prevention of ARF in blacks in sub-Saharan Africa is primarily concerned with the eradication of nephrotoxins and infections and a laxity in the abortion laws of the country. Only by an improvement in education, nutrition, socio-economic status and sanitation can one eradicate or diminish ARF in developing countries.

Three patients are described who presented with symptoms and signs of a vasculitic illness but in whom a definite diagnosis was not made until the application of a test to detect auto-antibodies to neutrophil cytoplasmic antigens. There has long been a need for a diagnostic marker for the groups of diseases which fall into the broad classification of systemic vasculitides. Diagnosis of the patients as having either Wegener's granulomatosis or microscopic polyarteritis by the finding of this auto-antibody enabled a positive approach to treatment with combinations of immunosuppressive agents. In addition, serial measurement of the auto-antibody titres enabled monitoring of disease activity.

Over a 5-year period 14 patients with acromegaly and gigantism were seen at the endocrine clinic of King Edward VIII Hospital: 9 were Blacks and 5 Indians; 8 of the patients were women. The mean age of the patients was 46 years. Surprisingly, only 2 patients complained of acral overgrowth. Symptomatology was varied and not characteristic of the condition. On examination all patients had unequivocal signs of soft-tissue and bony overgrowth, 64% had visual abnormalities and 50% hypertension. Radiologically, 88% showed an enlarged pituitary fossa. On biochemical investigation, the fasting levels of growth hormone (GH) were increased in 12 patients and during oral glucose tolerance tests, the GH levels in these 12 patients were not suppressed. One patient in whom the fasting GH level was not increased had progressed to the stage of panhypopituitarism, in the remaining patient challenge with thyrotrophin-releasing hormone (TRH) led to increased GH levels and L-dopa challenge resulted in a paradoxical decrease in GH levels. Seven patients with increased GH levels who were challenged with L-dopa showed the typical decrease in GH levels found in this condition; in 5 of these patients, challenged with TRH, GH levels increased. The findings emphasize that despite the ease of clinical diagnosis, appropriate biochemical investigations are necessary to confirm the exact status of the disease, which is rare in the population studied.

Crescentic glomerulonephritis is invariably associated with a fulminant syndrome of rapidly progressive renal failure which generally progresses to end-stage renal failure within weeks or months of onset. A widely differing aetiological background has been reported from Western countries. Work from the African continent is sparse. In a study from the province of Natal in South Africa between 1981 and 1987, 27 cases of crescentic nephritis were identified from a total of 458 patients who underwent renal biopsy at King Edward VIII and Addington hospitals. Poststreptococcal nephritis was the commonest aetiological factor (n = 8). There were six black patients in this group. Nine patients were classified as idiopathic and of these five were black. Four patients (one black) had antiglomerular basement membrane disease. Of the 24 patients subjected to variable combinations of immunosuppression, antiplatelet agents, dialysis and plasmapheresis, 11 improved, observed over four months to four years. Oliguria and severe renal failure at presentation signified a poor prognosis.

In 56 patients in whom the glomerular filtration rate (GFR) was estimated by the 51Cr-EDTA technique, serum creatinine and beta 2-microglobulin levels were also measured. In the 15 patients with a GFR of greater than or equal to 80 ml/min, both serum creatinine and beta 2-microglobulin levels were within the reference range. However, the beta 2-microglobulin level was elevated (greater than 2,3 mg/l) in all 41 patients with a GFR of less than 80 ml/min, while the serum creatinine level was increased (greater than 133 mumol/l) in only 35 patients. In the remaining 6 patients, the creatinine values ranged from 75 to 125 mumol/l. It would therefore seem that serum beta 2-microglobulin assay is a more sensitive test than creatinine assay for detecting impaired renal function.

IgA nephropathy besides exhibiting a characteristic geographical distribution has been noted to have a low incidence in the blacks of the USA. There is a paucity of data on IgA nephropathy in the blacks of Africa. We report our findings among the blacks and compare these with Indians. An analysis of the primary glomerular diseases of 252 blacks and 75 Indians over 6 years (1981-1986) was done. Mesangiocapillary glomerulonephritis was the commonest type in the black (35.7%), whereas mesangial proliferative glomerulonephritis was the commonest in Indians (26.7%). IgA nephropathy occurred in 2 blacks (1 male, 1 female), whereas there were 10 Indians (8 males, 2 females). Available data among whites in Natal show that IgA nephropathy is not uncommon. HLA studies done in blacks with IgA nephropathy did not reveal the HLAB35 or the DR4 antigen. HLAB35 in our blacks is less common compared to Indians and whites of Durban. Thus, although glomerulonephritis is common in blacks, IgA nephropathy is rare. This suggests that infection which is common in our black population may not be responsible for the aetiology of IgA nephropathy. A dietary factor in the form of a high-fibre diet may protect the black population from IgA nephropathy. However, a genetic factor cannot be excluded.

Two cases of renal impairment caused by the deposition of monoclonal immunoglobulin light-chain determinants in the glomerular mesangium and basement membranes as well as in the tubular basement membranes of the kidney are described (light-chain nephropathy). Both cases were associated with myeloma. Examinations by light microscopy, immunohistochemistry and electron microscopy are also described. Differential diagnoses on light microscopy include diabetic glomerulosclerosis (Kimmelstiel-Wilson lesions), amyloidosis and mesangiocapillary glomerulonephritis type 1.

The GH responses to TRH and L-dopa were investigated in 14 Indian and African patients with untreated acromegaly. A positive response to L-dopa (greater than 50% change from basal) was obtained in 6 of the 14 patients tested while a positive response to TRH (greater than 100% change from basal) was found in 5 of 12 patients tested. While 9 patients responded to at least one agent, only 2 had a positive response to both agents. Positive responders appeared to be hyper-prolactinemic and have evidence of abnormal glucose tolerance as compared to nonresponders.