Nephrogenic Calciphylaxis Arising after Bariatric Surgery: A Case Series.

Nephrogenic calciphylaxis is associated with multiple risk factors including long-term dialysis dependence, hyperphosphatemia, hypercalcemia, parathyroid hormone derangements, vitamin K deficiency, obesity, diabetes mellitus, warfarin use, and female sex. Bariatric surgery is known to cause altered absorption, leading to mineral and hormonal abnormalities in addition to nutritional deficiency. Prior case reports on calciphylaxis development following bariatric surgery have been published, though are limited in number. We report a case series of five bariatric patients from a single institution who developed nephrogenic calciphylaxis between 2012 and 2018. These patients had a history of bariatric surgery, and at the time of calciphylaxis diagnosis, demonstrated laboratory abnormalities associated with surgery including hypercalcemia (n = 3), hyperparathyroidism (n = 2), hypoalbuminemia (n = 5), and vitamin D deficiency (n = 5), in addition to other medication exposures such as vitamin D supplementation (n = 2), calcium supplementation (n = 4), warfarin (n = 2), and intravenous iron (n = 1). Despite the multifactorial etiology of calciphylaxis and the many risk factors present in the subjects of this case series, we submit that bariatric surgery represents an additional potential risk factor for calciphylaxis directly stemming from the adverse impact of malabsorption and overuse of therapeutic supplementation. We draw attention to this phenomenon to encourage early consideration of calciphylaxis in the differential for painful skin lesions arising after bariatric surgery as swift intervention is essential for these high-risk patients.

The effect of levocarnitine supplementation on dialysis-related hypotension: A systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: Dialysis patients have been shown to have low serum carnitine due to poor nutrition, deprivation of endogenous synthesis from kidneys, and removal by hemodialysis. Carnitine deficiency leads to impaired cardiac function and dialysis-related hypotension which are associated with increased mortality. Supplementing with levocarnitine among hemodialysis patients may diminish incidence of intradialytic hypotension. Data on this topic, however, lacks consensus. METHODS: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to 19th November 2021 to identify randomized controlled studies (RCTs), which examined the effects of oral or intravenous levocarnitine (L-carnitine) on dialysis-related hypotension among hemodialysis patients. The secondary outcome was muscle cramps. Study results were pooled and analyzed utilizing the random-effects model. Trial sequential analysis (TSA) was performed to assess the strength of current evidence. RESULTS: Eight trials with 224 participants were included in our meta-analysis. Compared to control group, L-carnitine reduced the incidence of dialysis-related hypotension among hemodialysis patients (pooled OR = 0.26, 95% CI [0.10-0.72], p = 0.01, I2 = 76.0%). TSA demonstrated that the evidence was sufficient to conclude the finding. Five studies with 147 participants showed a reduction in the incidence of muscle cramps with L-carnitine group (pooled OR = 0.22, 95% CI [0.06-0.81], p = 0.02, I2 = 74.7%). However, TSA suggested that further high-quality studies were required. Subgroup analysis on the route of supplementation revealed that only oral but not intravenous L-carnitine significantly reduced dialysis-related hypotension. Regarding dose and duration of L-carnitine supplementation, the dose > 4,200 mg/week and duration of at least 12 weeks appeared to prevent dialysis-related hypotension. CONCLUSION: Supplementing oral L-carnitine for at least three months above 4,200 mg/week helps prevent dialysis-related hypotension. L-carnitine supplementation may ameliorate muscle cramps. Further well-powered studies are required to conclude this benefit.

Calciphylaxis in a renal transplant recipient with normal graft function: A case report and review of literature.

Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare, life-threatening complication of end-stage renal disease. However, it may also occur in patients without renal failure, the nonuremic calciphylaxis. Most patients present with painful skin ulcers. Delayed diagnosis can lead to sepsis-related morbidity and mortality. Aberrations in calcium, phosphate, and parathyroid hormone physiology are common and biopsy is diagnostic. Early diagnosis and correction of vascular and metabolic aberrations may assist in healing as may the use of sodium thiosulfate and hyperbaric oxygen therapy. We report on successful treatment of a case of calciphylaxis in a renal transplant recipient with normal allograft function.

Vitamin K in Chronic Kidney Disease.

Vitamin K is a composite term referring to a group of fat-soluble vitamins that function as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX), which activates a number of vitamin K-dependent proteins (VKDPs) involved in haemostasis and vascular and bone health. Accumulating evidence demonstrates that chronic kidney disease (CKD) patients suffer from subclinical vitamin K deficiency, suggesting that this represents a population at risk for the biological consequences of poor vitamin K status. This deficiency might be caused by exhaustion of vitamin K due to its high requirements by vitamin K-dependent proteins to inhibit calcification.

Sickle Cell Nephropathy in the Pediatric Population.

BACKGROUND: Compared to the past, patients with sickle cell disease (SCD) currently live longer due to improvements in diagnosis and comprehensive care. Due to these advances, long-term chronic complications pose a greater challenge in the management of patients with SCD. In particular, sickle cell nephropathy (SCN) is associated with significant morbidity and mortality across all age groups. Furthermore, SCN is an understudied condition with relatively few symptoms and therefore requires close surveillance. In this review, we sought to explore the epidemiology, natural history, and treatment options for SCN with an emphasis on the pediatric population. SUMMARY: SCN invariably begins in childhood with evidence of structural changes detected as early as infancy. These indolent changes can progress undetected to advanced chronic kidney disease by late adolescence or early adulthood. The risk factors for progression are not well defined, but significant albuminuria (which is also the most common presentation in childhood) is a key factor in progression. One of the main challenges in understanding SCN in children is the poor correlation between estimated and measured glomerular filtration rates. Another challenge is the lack of large-scale longitudinal studies that track the clinical outcomes of pediatric patients over time. Several studies aim to identify early biomarkers of SCN in children, as albuminuria presents only following significant chronic damage. The utility of angiotensin converting enzyme inhibitors and hydroxyurea in treating albuminuria is addressed here as well as novel treatments that may be of benefit.

Calciphylaxis-as a drug induced adverse event.

INTRODUCTION: Calciphylaxis is a rare but devastating disease with a mortality rate up to 50% in 1 year. It is characterized by profoundly painful ischemic skin lesions and vascular calcification that affects predominantly patients with end stage renal disease. The use of certain medications is an important modifiable risk factor in calciphylaxis and discontinuation of these is a mainstay of treatment. AREAS COVERED: This review will provide an overview of calciphylaxis and will focus on how certain therapeutic agents can affect the risk of calcification and associated thrombosis, key processes involved in the development of calciphylaxis. EXPERT OPINION: Calciphylaxis treatment requires a multi-modal approach including prevention, risk factor management, wound care, reperfusion, and use of fibrinolytics and antioxidants. Patients with end stage renal disease represent the most affected population. This population often has multiple medications prescribed, some worth reconsidering before starting or continuing them. When possible, we recommend stopping all potentially contributing medications in patients with calciphylaxis, including warfarin, active vitamin D, calcium supplements, and iron.

Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis.

Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; P=0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses (ß=-8.99; P=0.04). In conclusion, vitamin K deficiency-mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study.

Interventions for lowering plasma homocysteine levels in kidney transplant recipients.

BACKGROUND: Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy. OBJECTIVES: To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Data was to be pooled using the random effects model. MAIN RESULTS: The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for a mean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 µmol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), all-cause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality. AUTHORS' CONCLUSIONS: There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients.

Nutritional vitamin D supplementation in dialysis: a randomized trial.

BACKGROUND AND OBJECTIVES: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency is common in patients initiating long-term hemodialysis, but the safety and efficacy of nutritional vitamin D supplementation in this population remain uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, placebo-controlled, parallel-group multicenter trial compared two doses of ergocalciferol with placebo between October 2009 and March 2013. Hemodialysis patients (n=105) with 25(OH)D levels ≤32 ng/ml from 32 centers in the Northeast United States were randomly assigned to oral ergocalciferol, 50,000 IU weekly (n=36) or monthly (n=33), or placebo (n=36) for a 12-week treatment period. The primary endpoint was the achievement of vitamin D sufficiency (25[OH]D >32 ng/ml) at the end of the 12-week treatment period. Survival was assessed through 1 year. RESULTS: Baseline characteristics were similar across all arms, with overall mean±SD 25(OH)D levels of 21.9±6.9 ng/ml. At 12 weeks, vitamin D sufficiency (25[OH]D >32 ng/ml) was achieved in 91% (weekly), 66% (monthly), and 35% (placebo) (P<0.001). Mean 25(OH)D was significantly higher in both the weekly (49.8±2.3 ng/ml; P<0.001) and monthly (38.3±2.4 ng/ml; P=0.001) arms compared with placebo (27.4±2.3 ng/ml). Calcium, phosphate, parathyroid hormone levels, and active vitamin D treatment did not differ between groups. All-cause and cause-specific hospitalizations and adverse events were similar between groups during the intervention period. Lower all-cause mortality among ergocalciferol-treated participants was not statistically significant (hazard ratio, 0.28; 95% confidence interval, 0.07 to 1.19). CONCLUSIONS: Oral ergocalciferol can increase 25(OH)D levels in incident hemodialysis patients without significant alterations in blood calcium, phosphate, or parathyroid hormone during a 12-week period.

The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis.

OBJECTIVE: To systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011. STUDY SELECTION: Randomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and assessing the effect of folic acid based homocysteine lowering therapy. No language restrictions were applied. DATA EXTRACTION: Two reviewers independently extracted data on study setting, design, and outcomes using a standardised form. The primary endpoint was cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality, or as defined by study author). Secondary endpoints included the individual composite components, all cause mortality, access thrombosis, requirement for renal replacement therapy, and reported adverse events, including haematological and neurological events. The effect of folic acid based homocysteine lowering on outcomes was assessed with meta-analysis using random effects models. RESULTS: 11 trials were identified that reported on 4389 people with chronic kidney disease, 2452 with end stage kidney disease, and 4110 with functioning kidney transplants (10,951 participants in total). Folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P = 0.326) or any of the secondary outcomes. There was no evidence of heterogeneity in subgroup analyses, including those of kidney disease category, background fortification, rates of pre-existing disease, or baseline homocysteine level. The definitions of chronic kidney disease varied widely between the studies. Non-cardiovascular events could not be analysed as few studies reported these outcomes. CONCLUSIONS: Folic acid based homocysteine lowering does not reduce cardiovascular events in people with kidney disease. Folic acid based regimens should not be used for the prevention of cardiovascular events in people with kidney disease.