Rapidly Progressive and Catastrophic Calciphylaxis After Mechanical Valve Replacement: An Anticoagulation Dilemma.

Warfarin is the only approved anticoagulant after mechanical valve replacement, but it is a well described risk factor for calciphylaxis among patients with end-stage kidney disease. Our patient with end-stage kidney disease rapidly developed calciphylaxis after dual mechanical valve replacement in association with warfarin initiation, posing significant challenges in clinical management and a fatal outcome. (Level of Difficulty: Intermediate.).

Treatment of secondary hyperparathyroidism: How do cinacalcet and etelcalcetide differ?

Secondary hyperparathyroidism (SHPT), commonly encountered in patients receiving maintenance dialysis, is associated with numerous adverse outcomes, including mortality. Calcimimetics, agents that act on the calcium sensing receptor (CaSR), were designed to overcome limitations in the use of vitamin D sterols to treat SHPT, and have demonstrated efficacy in reducing levels of PTH in randomized trials. Currently available calcimimetics include oral cinacalcet and the recently approved intravenously administered agent, etelcalcetide. While cinacalcet is an allosteric modulator of the CaSR, etelcalcetide acts as a direct CaSR agonist. Etelcalcetide's properties allow it to be administered intravenously thrice weekly at the end of a hemodialysis treatment session. Etelcalcetide has recently been shown to be more potent than cinacalcet in reducing PTH levels. However, etelcalcetide appears, like cinacalcet, to cause gastrointestinal intolerance. Additionally, etelcalcetide, which appears to reduce calcium substantially more than cinacalcet does, can prolong the QTc electrocardiographic interval. While etelcalcetide is very effective at reducing PTH levels, the current climate of dialysis cost containment in the United States may limit its widespread use. This review compares and contrasts the pharmacologic characteristics of cinacalcet and etelcalcetide, discusses the results of clinical trials involving these drugs, and posits implications for their use for clinical practice.

Managing hyperparathyroidism in hemodialysis: role of etelcalcetide.

Secondary hyperparathyroidism (SHPT) is common in patients receiving maintenance hemodialysis and is associated with adverse outcomes. Currently, SHPT is managed by reducing circulating levels of phosphate with oral binders and parathyroid hormone (PTH) with vitamin D analogs and/or the calcimimetic cinacalcet. Etelcalcetide, a novel calcimimetic administered intravenously (IV) at the end of a hemodialysis treatment session, effectively reduces PTH in clinical trials when given thrice weekly. Additional clinical effects include reductions in circulating levels of phosphate and FGF-23 and an improved profile of markers of bone turnover. However, despite being administered IV, etelcalcetide appears to be associated with rates of nausea and vomiting comparable to those of cinacalcet. Additionally, etelcalcetide, relative to placebo, causes hypocalcemia and prolonged electrocardiographic QT intervals, effects that must be considered when contemplating its use. Etelcalcetide likely has a role in treating hemodialysis patients with uncontrolled SHPT or with hypercalcemia or hyperphosphatemia receiving activated vitamin D compounds. However, its use should be at least partially constrained by consideration of the risk of hypocalcemia and resultant prolonged QT intervals in vulnerable patients. Because of its effectiveness as a PTH-reducing agent administered in the dialysis unit, etelcalcetide represents a potentially promising new therapeutic approach to the often vexing problem of SHPT in hemodialysis patients. However, whether its use is associated with changes in surrogate clinical end points, such as effects on rates of parathyroidectomy, fracture, vascular calcification, or mortality or on quality of life, remains to be studied.

The role of parathyroidectomy in the management of secondary hyperparathyroidism.

PURPOSE OF REVIEW: Parathyroidectomy (PTX) is often used to treat severe secondary hyperparathyroidism (SHPT) in patients receiving maintenance dialysis. However, most evidence for the proposed benefits of PTX originates from observational studies, which cannot demonstrate causality. A reconsideration of the potential role of PTX might help guide its appropriate use. RECENT FINDINGS: Several large observational studies have suggested that PTX can reduce mortality risk. However, these studies generally suffer from bias and confounding, tempering conclusions and suggesting that the true effects of PTX may not be known. PTX has been reported to be associated with a 2% 30-day mortality, a substantial risk for what is generally an elective procedure. Additionally, biochemical control after PTX in a subset of patients may be suboptimal. The optimal surgical approach to PTX in specific clinical scenarios is also uncertain. SUMMARY: PTX may be beneficial for certain patients with severe SHPT and clinical symptoms, but identifying patients in whom the benefits are likely to outweigh the risks is a substantial challenge. Further, great care must be taken to monitor symptoms and laboratory values in patients who undergo PTX in the immediate postoperative period and, in many cases, well beyond.

Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline.

BACKGROUND: Optimum management to prevent recurrent kidney stones is uncertain. PURPOSE: To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. DATA SOURCES: MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). STUDY SELECTION: 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. DATA EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. DATA SYNTHESIS: In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. LIMITATIONS: Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. CONCLUSION: In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Localization of discoidin domain receptors in rat kidney.

BACKGROUND/AIM: The discoidin domain receptors (DDRs) DDR1 and DDR2 are cardinal members of a receptor tyrosine kinase subfamily, activated by collagens. They are candidate effectors in tissue injury and fibrosis. We investigated the DDR expression in normal and remnant rat kidneys. METHODS: The DDR expression in kidney and other tissues was examined by indirect immunofluorescence, immunoblotting, and ribonuclease protection assays. The expression patterns in remnant and control kidneys were compared at 2-, 4-, and 8-week time points, following induction of injury. RESULTS: DDR1 is expressed in basolateral membranes of select nephron segments, from the connecting tubule to the renal papilla. DDR2 is expressed in apical membranes of select nephron segments, from the loop of Henle to the macula densa. The DDR1 protein expression is upregulated within the glomeruli of remnant kidneys. The distribution of DDR2 in remnant kidneys is similar to that in controls. The DDR mRNA levels in remnant and control kidneys were not significantly different, at any time point. CONCLUSIONS: The DDR1 localization in the rat kidney is consistent with roles in cell-matrix interactions. Upregulation within glomeruli of remnant kidneys suggests the possibility of additional roles in kidney injury. The DDR2 localization in adult rat kidneys is inconsistent with roles in cell-matrix interactions.