Itzchak Slotki

The practice of intravenous iron supplementation has grown as nephrologists have gradually moved away from the liberal use of erythropoiesis-stimulating agents as the main treatment for the anemia of CKD. This approach, together with the introduction of large-dose iron preparations, raises the future specter of inadvertent iatrogenic iron toxicity. Concerns have been raised in original studies and reviews about cardiac complications and severe infections that result from long-term intravenous iron supplementation. Regarding the iron preparations specifically, even though all the currently available preparations appear to be relatively safe in the short term, little is known regarding their long-term safety. In this review we summarize current knowledge of iron metabolism with an emphasis on the sources and potentially harmful effects of labile iron, highlight the approaches to identifying labile iron in pharmaceutical preparations and body fluids and its potential toxic role as a pathogenic factor in the complications of CKD, and propose methods for its early detection in at-risk patients.

Evaluating effect of obesity per se and the metabolic syndrome as a whole on the risk of developing chronic kidney disease (CKD) is key factor in developing a comprehensive public health approach to reduce morbidity and healthcare resource consumption. While there is considerable evidence to support increased risk of CKD in obese individuals and those with the metabolic syndrome, this relationship may be influenced by several factors. These include confounding variables, anthropometric measures, the end-point studied (e.g. development of early stage CKD, progression to end-stage renal disease or mortality), and the complex interrelationship between the various components of the metabolic syndrome. The study by Cao et al. in the current issue of BMC nephrology examines the impact of obesity on CKD risk in people with and without co-existing metabolic syndrome. The findings of this large, prospective study illustrate a clear correlation between increased body mass index (BMI) and risk of CKD regardless of whether or not there is co-existing metabolic syndrome. While the presence of the metabolic syndrome confers some additional risk of CKD in overweight and obese individuals, its effect is relatively modest and accounts for only 26 % of the risk associated with increased BMI. We discuss the complex epidemiological and methodological context in which these important findings should be understood, and their implications for public health and for individual patients and healthcare practitioners.

A high incidence and adverse outcomes of cognitive impairment in dialysis patients have recently become recognized. Classical risk factors, uremia, anemia, metabolic disturbances, and hemodynamic instability during dialysis accelerate vascular cognitive impairment. To evaluate laboratory factors that influence cognitive function in consecutive chronic hemodialysis (CHD) patients over a 2-year period. Between June 2010 and June 2011 we conducted a prospective, single-center trial that evaluated cognitive function in adult chronic hemodialysis (HD) patients. A battery of cognitive function tests was used: modified mini mental state (3MS), trailmaking tests A (trails A) and B (trails B). The 15-item geriatric depression scale (GDS) and the activities of daily living (ADL) test were used, respectively, for assessing symptoms of depression and global functional status. All tests were performed twice at yearly intervals in consecutive HD patients. Global cognitive impairment was defined as a 3MS < 80 and impaired executive function as a Trails A performance time > 75 seconds and Trails B > 180 seconds. 56 chronic HD patients aged 65.00 ± 17.8 years were studied; 57% of them were males. 86% suffered from hypertension (HTN), 40% were diabetics and ~ 1/3 had ischemic heart disease, congestive heart failure (CHF), and dyslipidemia. Average plasma calcium, phosphorus, and PTH were within the recommended range. No features suggestive of malnutrition, severe anemia, inflammation, or inadequate dialysis were detected. 14 patients (24%) had mild chronic hyponatremia (Na ranges 131 - 135 meq/L). Significant disturbances in global cognitive and executive function were detected in the study patients. In 2010, 50% had 3MS < 80, 71% and 91% had severely impaired trails A and B tests (respectively), 54% had symptoms of depression and 50% suffered from impaired ADL. Retesting of the survivors in 2011 revealed increased prevalence of cognitive and functional declines along with worsening depression scoring. Univariate analysis demonstrated significant correlation between cognitive decline and age, female gender, education, poor executive and functional status, inadequate dialysis dose (Kt/V < 1.2, p = 0.023), high plasma phosphorus levels (p > 6 mg/dL, p = 0.034), and hyponatremia (Na < 135 mEq/L, p = 0.001). Multivariate stepwise logistic regression analysis revealed statistically significant associations between hyponatremia and impaired ADL (p = 0.043) and impaired ADL and mortality (p = 0.002). A high prevalence of global cognitive and executive impairment was detected in our hemodialysis cohort. We found an association between mild chronic hyponatremia and impaired functional status. Whether treatments aimed at modifying hyponatremia could mitigate functional decline or mortality remains to be elucidated.

Background and Objectives. Hypoparathyroidism in patients with functioning kidneys leads to hyperphosphatemia. This article reviews data suggesting that hypoparathyroidism in patients on dialysis leads to hypophosphatemia. Design. Clinical data of the following were reviewed: (a) a patient with hypoparathyroidism before and during chronic dialysis; (b) patients on dialysis with surgically created hypoparathyroidism; (c) dialysis patients being treated with Cinacalcet, a calcium-sensing receptor agonist that lowers parathyroid hormone (PTH) levels; and (d) dialysis patients being treated with Velcalcetide, a new calcium-sensing receptor agonist that also lowers PTH. Results. In the patient presented in this study, in patients with surgically created hypoparathyroidism, and those receiving Cinacalcet or Velcalcetide, a fall in PTH was associated with hypophosphatemia or a fall in serum phosphorus. Conclusion. In patients on dialysis, hypoparathyroidism may lead to hypophosphatemia.

Colistin (polymyxin E) was developed ~ 60 years ago but was rarely used in clinical practice during the last 20 years because of concerns related to high rates of nephrotoxicity. However, it was recently reintroduced to clinical practice in many parts of the world for the treatment of multi-drug resistant gram-negative bacilli. In the current study, we evaluated the predictive capacity of urine neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of acute kidney injury (AKI) in geriatric patients with urinary tract infection (UTI) receiving colistin therapy. We studied 116 patients aged 80.7 ± 12 treated with colistin who suffered from UTI. Urinary NGAL was measured at baseline and 1 - 2 hours after the second dose of colistin. The primary outcome was AKI. Secondary outcome was in-hospital morbidity and mortality. 52 patients (44.8%) developed acute tubular necrosis (ATN) (14% of these had underlying CKD), 8 (7%) had prerenal azotemia, 8 (7%) had stable CKD without changes in renal function during hospitalization and the remaining 48 patients (41%) had normal kidney function. The mean duration of colistin therapy was 9.1 ± 4.8 days. At baseline, urine NGAL was 405 ± 452 g/l in ATN, 285 ± 256 g/l in prerenal azotemia, 390 ± 468 g/l in CKD and 347 ± 877 g/l in normal kidney function patients (difference non-significant). We were unable to demonstrate statistically significant increments of urine NGAL following colistin administration in either ATN or non-ATN patient groups. Urine NGAL was not correlated with urinary leukocyte or erythrocyte counts or baseline comorbidities such as CKD, heart failure, or diabetes. For primary outcome (ATN), receiver operating characteristics curve revealed AUC 0.59 (95% CI 0.49 - 0.7) sensitivity 0.65, and specificity 0.62 for a cutoff value of urinary NGAL 140 g/l. Similar results were obtained for secondary outcomes. Our data suggest limited predictive capacity of urinary NGAL for early diagnosis of AKI in a large clinical setting of geriatric patients hospitalized for UTI and receiving the potentially nephrotoxic colistin. This finding is likely due to the powerful influence of UTI on NGAL levels in both patients with normal kidney function and those with a wide spectrum of acute or chronic kidney diseases.

While dialysis historically began as treatment intended for younger patients, it has, over time, increasingly been extended to treat elderly patients with a high comorbidity burden. Data on the outcomes of dialysis in these patients show that in some cases it confers no benefit and may be associated with functional decline. We describe a 101-year-old male patient with chronic kidney disease (CKD), admitted to the intensive care unit (ICU) with exacerbation of heart failure and sepsis. He experienced acute deterioration of renal function, with oliguria and acidosis. The patient's healthcare proxy insisted that dialysis be initiated despite his extremely advanced age, citing the patient's devout religious beliefs. He underwent 56 dialysis treatments over the course of ∼4 months after which he died as a result of septic and cardiogenic shock. Our case is unique, in that it may represent the oldest individual ever reported to start haemodialysis. It illustrates the ever-growing clinical and ethical challenges posed by the treatment of renal failure in the geriatric population.