Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has been resurrected as a potential contributory risk factor in the development and progression of CKD. Most studies documented that an elevated serum uric acid level independently predicts the development of CKD. Raising the uric acid level in rats can induce glomerular hypertension and renal disease as noted by the development of arteriolosclerosis, glomerular injury and tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD. While further clinical trials are necessary, uric acid is emerging as a potentially modifiable risk factor for CKD. Gout was considered a cause of CKD in the mid-nineteenth century [1], and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients. In their large series of gouty subjects Talbott and Terplan found that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis, glomerulosclerosis and interstitial fibrosis) [2]. Additional studies showed that during life impaired renal function occurred in half of these subjects [3]. As many of these subjects had urate crystals in their tubules and interstitium, especially in the outer renal medulla, the disease became known as gouty nephropathy. The identity of this condition fell in question as the presence of these crystals may occur in subjects without renal disease; furthermore, the focal location of the crystals could not explain the diffuse renal scarring present. In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se [4]. Indeed, gout was removed from the textbooks as a cause of CKD, and the common association of hyperuricemia with CKD was solely attributed to the retention of serum uric acid that is known to occur as the glomerular filtration rate falls. Renewed interest in uric acid as a cause of CKD occurred when it was realized that invalid assumptions had been made in the arguments to dismiss uric acid as a risk factor for CKD [5]. The greatest assumption was that the mechanism by which uric acid would cause kidney disease would be via the precipitation as crystals in the kidney, similar to the way it causes gout. However, when laboratory animals with CKD were made hyperuricemic, the renal disease progressed rapidly despite an absence of crystals in the kidney [6]. Since this seminal study, there has been a renewed interest in the potential role uric acid may have in both acute and CKD. We briefly review some of the major advances that have occurred in this field in the last 15 years.

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

The prevalence of chronic kidney disease (CKD) has increased and will continue to increase in the United States and worldwide. This is alarming considering that CKD is an irreversible condition and patients who progress to chronic kidney failure have reduced quality of life and high mortality rates. As such, it is imperative to identify modifiable risk factors to develop strategies to slow CKD progression. One such factor is hyperuricemia. Recent observational studies have associated hyperuricemia with kidney disease. In addition, hyperuricemia is largely prevalent in patients with CKD. Data from experimental studies have shown several potential mechanisms by which hyperuricemia may contribute to the development and progression of CKD. In this article, we offer a critical review of the experimental evidence linking hyperuricemia to CKD, highlight gaps in our knowledge on the topic as it stands today, and review the observational and interventional studies that have examined the potential nephroprotective effect of decreasing uric acid levels in patients with CKD. Although uric acid also may be linked to cardiovascular disease and mortality in patients with CKD, this review focuses only on uric acid as a potential therapeutic target to prevent kidney disease onset and progression.

Chronic kidney disease (CKD) is a growing global health problem. CKD is typically associated with a prothrombotic tendency in the early stages of the disease, whereas in its more advanced stage, that is, end-stage renal disease, patients suffer from a prothrombotic tendency and, in many cases, a bleeding diathesis. The exact etiology behind the coexistence of these conflicting hemostatic disorders is poorly understood. This review critically appraises studies examining the abnormalities in the hemostasis pathway in patients with CKD, as well as the therapeutic options that are currently available to treat these individuals.

Obesity is a risk factor for hypertension, diabetes mellitus (DM), dyslipidemia, and hyperuricemia. Here, we evaluated whether the same body mass index (BMI) for the U.S. population conferred similar metabolic risk in Japan. This was a cross-sectional analysis involving 90,047 Japanese adults (18–85 years) from St. Luke’s International Hospital, Tokyo, Japan and 14,734 adults from National Health and Nutrition Examination Survey (NHANES) collected in the U.S. We compared the prevalence of hypertension, DM, dyslipidemia, and hyperuricemia according to BMI in Japan and the U.S. The prevalence of hypertension, DM, and dyslipidemia were significantly higher in the U.S. than Japan, whereas the prevalence of hyperuricemia did not differ between countries. Higher BMI was an independent risk factor for hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and in the U.S. after adjusting for age, sex, smoking and drinking habits, chronic kidney disease, and other cardiovascular risk factors. The BMI cut-off above which the prevalence of these cardio-metabolic risk factors increased was significantly higher in the U.S. than in Japan (27 vs. 23 kg/m² for hypertension, 29 vs. 23 kg/m² for DM, 26 vs. 22 kg/m² for dyslipidemia, and 27 vs. 23 kg/m² for hyperuricemia). Higher BMI is associated with an increased prevalence of hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and U.S. The BMI cut-off above which the prevalence of cardio-metabolic risk factors increases is significantly lower in Japan than the U.S., suggesting that the same definition of overweight/obesity may not be similarly applicable in both countries.