Oxalate nephropathy after pancreaticoduodenectomy: a case report.

A 75-year-old male developed acute kidney injury KDIGO stage 3 a few weeks after Whipple surgery was performed for a distal cholangiocarcinoma. Kidney biopsy revealed oxalate nephropathy. This was attributed to post-Whipple malabsorption, poor compliance with pancreatic enzyme replacement therapy, and daily intake of vitamin C supplements. Pancreatic enzyme replacement therapy was resumed and calcium carbonate initiated, with an improvement in glomerular filtration rate. Unfortunately, due to oncological progression, best supportive care was initiated.We review the pathophysiology and conditions predisposing to secondary hyperoxaluria and oxalate nephropathy. This diagnosis should be considered among the main causes of acute kidney injury following pancreatectomy, with important therapeutic implications.

Evaluation of the effect of sodium zirconium cyclosilicate on arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with hyperkalaemia: protocol for the multicentre, randomised, controlled DIALIZE-Outcomes study.

INTRODUCTION: Patients with kidney failure receiving chronic haemodialysis have elevated risk of arrhythmias potentially increasing the likelihood of sudden cardiac death, stroke and hospitalisation. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) was an efficacious and well-tolerated treatment for predialysis hyperkalaemia in patients undergoing haemodialysis. The DIALIZE-Outcomes study evaluates the effect of SZC on sudden cardiac death and arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with recurrent hyperkalaemia. METHODS AND ANALYSIS: International, multicentre, randomised, double-blind, placebo-controlled study conducted at 357 study sites across 25 countries. Adults (≥18 years) receiving chronic haemodialysis three times per week with recurrent predialysis serum potassium (K+) ≥5.5 mmol/L post long interdialytic interval (LIDI) are eligible. Patients (~2800) will be randomised 1:1 to SZC or placebo, starting at 5 g orally once daily on non-dialysis days and titrated weekly in 5 g increments (maximum 15 g) to target predialysis serum K+ 4.0-5.0 mmol/L post LIDI. The primary objective is to evaluate efficacy of SZC versus placebo in reducing occurrence of the primary composite endpoint of sudden cardiac death, stroke or arrhythmia-related hospitalisation, intervention or emergency department visit. Secondary endpoints include efficacy of SZC versus placebo in maintaining normokalaemia (serum K+ 4.0-5.5 mmol/L post LIDI) at the 12-month visit, preventing severe hyperkalaemia (serum K+ ≥6.5 mmol/L post LIDI) at the 12-month visit and reducing the incidence of individual cardiovascular outcomes. Safety of SZC will be evaluated. The study is event driven, with participants remaining in the study until 770 primary endpoint events have occurred. Average time in the study is expected to be ~25 months. ETHICS AND DISSEMINATION: Approval was obtained from the relevant institutional review board/independent ethics committee from each participating site (approving bodies in supplementary information). The results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: EudraCT 2020-005561-14 and clinicaltrials.gov identifier NCT04847232.

Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review.

Hyperoxaluria results from either inherited disorders of glyoxylate metabolism leading to hepatic oxalate overproduction (primary hyperoxaluria), or increased intestinal oxalate absorption (secondary hyperoxaluria). Hyperoxaluria may lead to urinary supersaturation of calcium oxalate and crystal formation, causing urolithiasis and deposition of calcium oxalate crystals in the kidney parenchyma, a condition termed oxalate nephropathy. Considerable progress has been made in the understanding of pathophysiological mechanisms leading to hyperoxaluria and oxalate nephropathy, whose diagnosis is frequently delayed and prognosis too often poor. Fortunately, novel promising targeted therapeutic approaches are on the horizon in patients with primary hyperoxaluria. Patients with secondary hyperoxaluria frequently have long-standing hyperoxaluria-enabling conditions, a fact suggesting the role of triggers of acute kidney injury such as dehydration. Current standard of care in these patients includes management of the underlying cause, high fluid intake, and use of calcium supplements. Overall, prompt recognition of hyperoxaluria and associated oxalate nephropathy is crucial because optimal management may improve outcomes.

The Micro-Elimination Approach to Eliminating Hepatitis C: Strategic and Operational Considerations.

The introduction of efficacious new hepatitis C virus (HCV) treatments galvanized the World Health Organization to define ambitious targets for eliminating HCV as a public health threat by 2030. Formidable obstacles to reaching this goal can best be overcome through a micro-elimination approach, which entails pursuing elimination goals in discrete populations through multi-stakeholder initiatives that tailor interventions to the needs of these populations. Micro-elimination is less daunting, less complex, and less costly than full-scale, country-level initiatives to eliminate HCV, and it can build momentum by producing small victories that inspire more ambitious efforts. The micro-elimination approach encourages stakeholders who are most knowledgeable about specific populations to engage with each other and also promotes the uptake of new models of care. Examples of micro-elimination target populations include medical patients, people who inject drugs, migrants, and prisoners, although candidate populations can be expected to vary greatly in different countries and subnational areas.

Chronic dialysis, NAT2 polymorphisms, and the risk of isoniazid-induced encephalopathy - case report and literature review.

BACKGROUND: Isoniazid is the most widely used anti-tuberculosis agent, yet it may lead to life-threatening complications. CASE PRESENTATION: Here we report the case of a chronic hemodialysis patient who developed severe encephalopathy after the start of isoniazid. Blood levels of isoniazid were elevated, and acetyl-isoniazid over isoniazid ratio was decreased 3 h after intake of the medication, suggesting that a slow acetylator phenotype may have contributed to drug toxicity, in addition to pyridoxal phosphate removal by dialysis. This hypothesis was confirmed by sequencing of NAT2, the gene responsible for isoniazid elimination, and identification of NAT2 polymorphisms compatible with a slow acetylator phenotype. Isoniazid withdrawal along with supplementation using high doses of pyridoxine successfully reversed the drug toxicity. Isoniazid toxicity occurs in populations at risk, including patients with chronic kidney failure or NAT2 polymorphisms, who have a disturbed metabolism of pyridoxine or isoniazid, respectively, and those on renal replacement therapies, in whom pyridoxal phosphate - the active metabolite of pyridoxine - is inadvertently removed by dialysis. CONCLUSIONS: Physicians should be aware of the increased risk of isoniazid toxicity in patients on dialysis and in those with a slow acetylator phenotype conferred by NAT2 polymorphisms. Adaptation of prescription - either with higher doses of pyridoxine or decreased doses of isoniazid, respectively - has been suggested to reduce the risk of potentially life-threatening toxicity of isoniazid.

Phosphate binder pill burden, patient-reported non-adherence, and mineral bone disorder markers: Findings from the DOPPS.

Because of multiple comorbidities, hemodialysis (HD) patients are prescribed many oral medications, including phosphate binders (PBs), often resulting in a high "pill burden." Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we assessed associations between PB pill burden, patient-reported PB non-adherence, and levels of serum phosphorus (SPhos) and parathyroid hormone (PTH) using standard regression analyses. The study included data collected from 5262 HD patients from dialysis units participating in the DOPPS in 12 countries. PB prescription ranged from a mean of 7.4 pills per day in the United States to 3.9 pills per day in France. About half of the patients were prescribed at least 6 PB pills per day, and 13% were prescribed at least 12 PB pills per day. Overall, the proportion of patients who reported skipping PBs at least once in the past month was 45% overall, ranging from 33% in Belgium to 57% in the United States. There was a trend toward greater PB non-adherence and a higher number of prescribed PB pills per day. Non-adherence to PB prescription was associated with high SPhos (>5.5 mg/dL) and PTH (>600 pg/mL). Adherence to PB is a challenge for many HD patients and may be related to the number of PB pills prescribed. Prescription of a simplified PB regimen could improve patient adherence and perhaps improve SPhos and PTH levels.

Potassium-binding resins: Associations with serum chemistries and interdialytic weight gain in hemodialysis patients.

BACKGROUND: Although potassium-binding sodium-based resins (K resins) have been prescribed to treat hyperkalemia for 50 years, there have been no large studies of their effects among hemodialysis (HD) patients. METHODS: Data from 11,409 patients in the Dialysis Outcomes and Practice Patterns Study in Belgium, Canada, France, Italy, and Sweden (nations where ≥5% of patients were prescribed a sodium- based K resin; seven other countries had <5% use) between 2002 and 2011 were analyzed. Linear mixed models examined associations between K resin use and interdialytic weight gain (IDWG) and serum electrolyte concentrations. Mortality was analyzed using Cox regression. An instrumental variable approach was used to partially account for unmeasured confounders. RESULTS: The K resin prescription rate was 20% overall. As hypothesized, patients prescribed a K resin had greater IDWG and higher serum bicarbonate, phosphorus, and sodium (but not calcium) concentrations. Patients prescribed a K resin had higher serum K levels, but serum K levels were lower in an instrumental variable analysis limiting treatment by indication bias. K resin use was not associated with mortality risk. CONCLUSION: We report the first large study of K resin use and associated laboratory and clinical outcomes in HD patients. The prescription rate of K resins varied dramatically by country and dialysis center. The results suggest that K resin use may effectively lower serum K, although at the expense of somewhat higher phosphatemia and greater IDWG, and had no clear association with mortality. Further study is warranted to elucidate the optimal role for K resins in modern dialysis care.

Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol.

BACKGROUND: Patients on haemodialysis (HD) exhibit increased cardiovascular mortality associated with accelerated vascular calcification (VC). VC is influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and supplementation with vitamin K reduces inactive MGP levels in these patients. The VitaVasK trial analyses whether vitamin K1 supplementation affects the progression of coronary and aortic calcification in HD patients. METHODS: VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score of at least 100 will be randomized to continue on standard care or to receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes in the volume scores at the 18-month MSCT versus the baseline MSCT). Secondary end points comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and all-cause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients.

The prevalence and detection of chronic kidney disease (CKD)-related metabolic complications as a function of estimated glomerular filtration rate in the oldest old.

BACKGROUND: The prevalence of CKD rises with age. The prevalence of CKD-related metabolic complications in the oldest old in relation to different GFR estimations is largely unknown. eGFR-based thresholds for the detection of these complications remain uncertain. METHODS: A cross-sectional analysis embedded within the BELFRAIL study, a population-based prospective cohort study of the oldest old in Belgium, was performed. The prevalence of anemia, elevated serum parathyroid hormone (PTH), high serum phosphorus and low uncorrected serum calcium was analyzed in relation to GFR estimated by three serum creatinine-based equations and one cystatin C-based equation. RESULTS: 567 patients aged 80 and over were included (63% women). The prevalence of anemia, elevated PTH and high phosphorus showed an inverse relationship with eGFR. This relationship remained after logistic regression analysis adjusting for demographics and co-morbidity. No such relationship between low calcium and eGFR was found. Using an eGFR of 60 ml/min/1.73 m(2) modification of diet in renal disease equation (MDRD) as screening threshold for metabolic complications would result in a high incidence of missed complications: 29%, 28% and 40% for anemia, elevated PTH and high phosphorus, respectively. CONCLUSION: The presence of anemia, an elevated PTH or an elevated serum phosphorus level increased with lower eGFR but even among patients with an eGFR >60 ml/min/1.73 m(2), these complications are common. Thus this eGFR cut-off appears inadequate for patients aged 80 and over. How the oldest old may be screened appropriately for these CKD-related complications requires further investigation.

Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Mineral metabolism has emerged as an important predictor of morbidity and mortality in dialysis patients, independent of bone and muscle concerns. Several expert panels have issued management guidelines for mineral metabolism. METHODS: The state of mineral metabolism (serum parathyroid hormone [PTH], phosphorus, calcium, and calcium-phosphorus product) was described for representative samples of patients and facilities from 7 countries (France, Germany, Italy, Japan, Spain, United Kingdom, and United States) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS I, 1996-2001; DOPPS II, 2002-2004). RESULTS: A relatively modest percentage of patients fell within the guideline range for PTH (21.4% in DOPPS I, 26.2% in DOPPS II), serum phosphorus (40.8%, 44.4%), albumin-corrected serum calcium (40.5%, 42.5%), and calcium-phosphorus product (56.6%, 61.4%). Results were not dramatically different across countries. The majority of patients not within guideline ranges had high serum levels of phosphorus (51.6% in DOPPS I, 46.7% in DOPPS II), calcium (50.1%, 48.6%), and calcium-phosphorus product (43.4%, 38.6%) and low (<150 pg/mL) concentrations of PTH (52.9%, 47.5%). It was rare for patients to fall within recommended ranges for all indicators of mineral metabolism; 23% to 28% fell within guideline for at least 3 measures and only 4.6% to 5.5% of patients were within range for all 4. The risks of all-cause and cardiovascular mortality were directly and independently associated with each of the 4 indicators. CONCLUSION: The DOPPS provides a useful comparison benchmark for the state of mineral metabolism management of patients with kidney disease; it also affirms the association between mineral metabolism and important patient outcomes.